LIBRARY OF CONGRESS. 





Shelf.. 



UNITED STATES OF AMERICA. 



NOTES 



ON 



THE LECTURES OF PROF. JOHN GUITERAS 



ON 



GENERAL and SPECIAL PATHOLOGY, 



Delivered before the Second and Third Year Students 
of the University of Pennsylvania, 



/ 

THE LECTURES OF DR. JOSEPH McFARLAND 



BACTERIOLOGY, 



Delivered before the Third Year Class. 







^3^ ^ 



/ ARRANGED BY 



Dr. William S. Carter and Dr. David Riesman, 

Quiz Masters In Pathology, 



\ 



X 






Avil Printing Company, 

3941-43-45 Market Street, 

Philadelphia. 



Copyright, 1895, 
By Avil Printing Co. 



© 






PREFACE. 



T N response to a frequently expressed desire on the part of the 

students, we have undertaken the publication of this volume of 
notes. During its preparation we have been stimulated by the 
interest and encouragement of Professor Guiteras, to whom we 
beg to acknowledge our grateful indebtedness. 

We are under obligations to Dr. Alfred Stengel for the cuts of 
many of the illustrations. 

By the kind permission of Dr. Joseph McFarland we have been 
able to add an epitome of his lectures on Bacteriology. 

We hope that the notes will assist the student in mastering the 
important subject of Pathology. 



CHAPTER I. 



Pathology is that branch of the science of medicine which 
concerns itself with the study of the manifestations of energy and 
the changes in structure which take place in a diseased living being. 
Broadly speaking, it is the science of disease. 

The term "disease" includes all those disturbances of the 
normal manifestations of life which impair, more or less, the adapta- 
bility of the individual to surrounding media. 

By " a disease" we understand a group of such modifications 
occurring with sufficient regularity of association to constitute a 
distinct species. 

Disease adds no new element to the body ; it merely modifies 
previously existing functions and structures. We deal, therefore, 
in pathology with two factors : the changes in the function, i. e. f 
the manifestations of energy, and the changes in the structure, of 
diseased organs or tissues. 

The first recognizable change is one affecting the structure. 
But we cannot conceive of such a change occurring without some 
antecedent force or cause to bring it about. This fundamental cause 
is believed to be certain obscure functional derangements which 
lead to modifications of structure, and these, in turn, to secondary 
changes of function. The last become recognizable to us as the 
symptoms of the disease. 

DIVISIONS OF PATHOLOGY. 

Analogous to the division of Biology into Morphology, 
Physiology, and Embryology, Pathology is divided into 
Morbid Anatomy, or the study of the changes of structure 
in disease, Morbid Physiology, the study of the changes of 
function in disease, and Etiology, the study of the causation 
of disease. Of these three branches morbid anatomy is the most 

• 5 



6 NOTES ON PATHOLOGY. 

advanced ; etiology is also highly developed, chiefly through the 
impetus which bacteriology has given to it ; morbid physiology, 
probably the' most important branch, is still very obscure. 
Pathology may be further divided into 

GENERAL AND SPECIAL PATHOLOGY. 

In general pathology we study disease from a general point 
of view ; we study those changes of function and structure that 
can occur in any organ, e.g., inflammation. In special pathology 
we study these changes as they occur in special organs, e. g., pneu- 
monia. 

GENERAL PATHOLOGY. 

Morbid processes are of two kinds : (a) Elementary or 
Simple — those in which the changes in the tissues are of one 
kind only, or those occurring in individual cells, e.g., fatty degen- 
eration. They are the elements of which disease is made up. 

(b) Compound — those composed of several elementary mor- 
bid processes ; e.g., inflammation. 

Morbid processes may be integrating or progressive, 
those in which there is a building up of tissue, or disintegrad- 
ing or retrograde, those in which tissues are destroyed. The 
former are exemplified by hypertrophy and hyperemia, the latter 
by atrophy and degenerations. 



SIMPLE MORBID PROCESSES. 

HYPERTROPHY. 

Hypertrophy is an increase in the size of a tissue or organ, 
taking place independently of the general growth of the organism 
and without any marked alteration in the outline of the organ. 

Normal Example. — Enlargement of the uterus during preg- 
nancy. 

Hypertrophy may be (i) general, affecting several parts of 
the body, or (2) local, limited to a single organ or part. Local 
hypertrophy is classified into (a) true or functional hypertrophy, and 
(b) false or pseudo-hypertrophy. 



HYPERTROPHY. 7 

True hypertrophy is a uniform enlargement of an organ affecting 
all the tissues, and is accompanied by an exaltation of function. It is 
caused by an increased functional demand upon the part, either 
directly, as in the uterus in pregnancy, or indirectly, when the 
demand on the organ is the result of the imperfect action of another, 
usually of a companion organ, as in hypertrophy of a kidney after 
the removal of its fellow, or the enlargement of one lung when the 
other is diseased. In false hypertrophy the tissue most apt to be 
increased is that least concerned in the function of the organ, 
i. e. t connective tissue. Hypertrophic cirrhosis of the liver, and 
pseudo-hypertrophic muscular paralysis are examples. 

Morbid Anatomy. — In true hypertrophy the outline of the 
organ is generally preserved; in false hypertrophy it is apt to 
undergo some change, owing to the presence of an excess of con- 
nective tissue. 

Hypertrophy is divided into (1) simple, or that in which there 
is an increase in the size of the individual cells, and (2) numerical, 
that in which there is an increase in the number of cells. The 
latter is the more common form, although both very frequently 
occur together. Simple hypertrophy is not easily demonstrated : 
we see it best in the pregnant uterus and in the hypertrophied 
heart. 

The term hyperplasia is used as a synonym of numerical 
hypertrophy ; it implies a multiplication of cells with a tendency to 
form new tissue. It does not necessarily lead to hypertrophy; 
indeed, it may cause atrophy, as in atrophic cirrhosis of the liver. 

The subject of numerical hypertrophy brings up the question 
as to the manner in which cell-proliferation takes place. It occurs 
in one of two ways — (1) by direct cell-division, or amitosis, or (2) 
by indirect cell-division, mitosis, karyomitosis, or karyokinesis. The 
latter is the more frequent and more important mode, and depends 
upon complicated changes in the filamentary substance of the nucleus. 
This substance is known as mitome, or, on account of the readiness 
with which it takes up the nuclear stains, hematoxylin, safranin, 
gentian-violet, etc., as chromatin. The inter-filamentary substance, 
staining poorly, is termed achromatin. 

The threads of the mitome are arranged in the form of U- 
shaped loops, the closed ends of which are all directed toward the 
same pole of the nucleus. 



8 NOTES ON PATHOLOGY. 

From these primary loops delicate secondary filaments are 
given off, which by their interlacing produce a dense, compact net- 
work. 

The essential changes preparatory to cell division take place in 
the loops. The process is usually divided into three stages : 

1. Concentration — the thickening of the primary and disap" 
pearance of the secondary filaments. 

2. Splitting of the filaments in their longitudinal axis. 

3. Rearrangement of the filaments — (a) Monaster, or mother- 
star, (b) Diaster, or daughter-star. 




At rest. First stage. Second stage. a Third stage, b 



When these changes are completed the cell protoplasm and 
the nucleus become constricted ; division then takes place, leaving 
two independent cells, each with its nucleus. Special methods ot 
preparation of tissues are necessary to show the appearances just 
described. The most important point is to " fix " the tissues as 
quickly as possible. For this purpose the pieces should be very 
fresh, should not exceed one-half c. cm. in size, and should im- 
mediately be immersed in a good fixing fluid, the best being 
Flemming's solution: 1 per-cent sol. chromic acid, 15 parts; 2 per- 
cent sol. osmic acid, 4 parts ; glacial acetic acid, 1 part. The tissue 
is left in this six to forty-eight hours ; it is then washed in running 
water three to six hours, and finally hardened in alcohol and 
imbedded. 

The sections are stained for from one to twenty-four hours in 
a one per-cent watery solution of safranin ; they are then briefly 
washed in water and differentiated in absolute alcohol containing a 
few drops of a one per-cent solution of hydrochloric acid in alcohol. 
When clouds of color cease to be given off the section is removed 
to absolute alcohol, thence to oil, and mounted. 

Under the microscope the nuclei undergoing karyokinetic 
changes are stained a dark reddish-brown, while the quiescent 
nuclei are light in color. The most striking appearance is the 
daughter-star 



ATROPHY. 9 

Clinical Causes. I . Increased functional activity. 

2. Congenital tendency, e. g., giant growth of certain parts. 

3. Removal of pressure. The growth of certain structures is 
kept within bounds by the pressure of adjacent organs. We com- 
monly find increased thickness of the skull in cases where parts of 
the brain are absent. 

4. Direct stimtdation, taking the form of intermittent pressure ; 
e. g., corns. Constant pressure leads to atrophy. 

5. Disturbances of nutrition, (a) Direct disturbances (trophic) 
of innervation, as thickening of the skin in some nerve lesions. 
(b) Interference with the function of certain obscure organs, viz., 
the thyroid gland, the thymus, the pituitary body, and probably 
the suprarenal capsules. 

There is a disease known as Acromegaly \ which is characterized 
by an enlargement of the extremities, chiefly the hands, and of the 
face. Both the bony and the soft parts are involved. In a num- 
ber of cases the disease was associated with pathologic changes in 
the pituitary body. 

ATROPHY. 

Atrophy is a diminution in the bulk of one or more of the 
component parts of an organ. Since the more important tissue- 
elements are usually affected, there is also a diminution of functional 
activity. Normal examples are the atrophy of the thymus gland 
in early life ; of the umbilical blood-vessels after birth ; and of the 
female reproductive organs at the menopause. There may be small- 
ness of size not due to atrophy. For example, an organ may be 
diminutive from an arrest of development, a condition termed 
hypoplasia. It is seen in chlorosis, in which we frequently find 
that the sexual organs and the heart and great vessels are abnorm- 
ally small. Total absence of an organ or a part of an organ is called 
aplasia or agenesis ; it gives rise to monstrosities. 

Morbid Physiology. — Atrophy is brought about either by 
an insufficiency in the food supply of the cells, or by an inability 
on the part of the cells to use the nutritive material brought to 
them. It is (a) simple, due to a diminution in the size of the cells, 
without marked change in their protoplasm, or (b) degenerative, 
due to a breaking down of the protoplasm of the cells. 

Morbid Anatomy. — (a) Macroscopy. An atrophic organ is 
smaller; its outline is usually retained, although the surface maybe 



io NOTES ON PATHOLOGY. 

irregular; the consistency is, as a rule, greater than normal, on 
account of a relative or absolute increase of the connective tissue ; 
its color is darker, from a relative excess of pigment ; frequently, 
too, new pigment is deposited, (b) Microscopy. The cells are dim- 
inished in size or degenerated ; the connective tissue is increased. 

Brown Atrophy occurs in organs the seat of chronic con- 
gestion, especially in the heart and liver. 

Clinical Causes. — I. Senile changes. — These are to a certain 
extent physiologic ; are pathologic when occurring early. They 
affect especially the testicle, heart and lungs (senile emphysema). 

2. Defective nutrition. 

(a) General, as in starvation. 

(3) Local deficiency of blood-supply, as from obstruction of 
an artery. 

3. Constant pressure, as atrophy of bones from pressure of an 
aneurysm. 

4. Disuse, as atrophy of muscles in ankylosis of a joint. 

5. Disturbances of innervation. Neuropathic atrophy. This 
is due to a loss of the trophic influence and is most strikingly 
exemplified by the atrophy of the muscles in acute anterior 
poliomyelitis, or infantile palsy, a disease affecting the ganglion 
cells of the anterior horns of the spinal cord. It is a degenerative 
atrophy. 

INFILTRATIONS AND DEGENERATIONS. 

Both imply retrograde changes in the cells, infiltration being 
the lowest one in the series of disintegrating processes. It con- 
sists in the deposit in the cell of an abnormal substance or of a 
normal constituent in excess. The nucleus and cell-protoplasm 
are pushed to one side and generally preserve their integrity. 
Degeneration is the conversion of the cell-protoplasm into an 
abnormal substance. It is a more serious process since it destroys 
the cell. 

The infiltrations are : Fatty, calcareous, pigmentary, serous, 
and glycogenic. 

FATTY INFILTRATION. 

This consists in the storage of excessive quantities of fat 
within the cell, the protoplasm remaining relatively intact. 

Normal examples are the adipose tissue and the liver. 
Pathologically, it occurs in the subcutaneous tissue, where, if general, 



FATTY INFILTRATION. n 

it is termed obesity or polysarcia ; in the liver, in the heart, around 
atrophic organs, etc. In obesity certain parts, as the eyelids, the alae 
nasi, the lobules of the ears, the lips, and the prepuce escape. His- 
tologically, the fatty deposit affects both the cells and the inter- 
cellular substance, the red corpuscles and the ganglion cells of the 
nervous system being alone exempt. 

Morbid Physiology*. — There exists in fatty infiltration a 
disturbance of the fat-building and fat-storing functions. The 
deposit of fat may be due to an excess of food ingested or to an 
impairment in the consumption of the fat normally brought to cell. 
Defective oxidation is at the bottom of the process. 

All food-stuffs, fats, albuminoids, and carbohydrates may give 
origin to the deposit of fat, particularly the last-named. 

The albuminous food may be converted into fat within the 
body ; thus, the cow which consumes but little fat produces a large 
quantity of it out of the vegetable proteids. Certain post-mortem 
changes also illustrate the derivation of fat from albuminous 
substances ; adipocere, a fatty material, may be formed out of the 
muscles after death. 

Animals fed on carbohydrates deposit fat. Bees produce wax 
out of the plant-sugar upon which they feed. How this conver- 
sion is brought about within the body is not known. 

Morbid Anatomy. — (a) Macroscopy. The size of the 
organ is increased, but the outline is preserved ; the consistency 
is usually diminished, yet it may not be greatly altered ; the color 
is yellowish, either uniformly or in streaks, the latter being the case 
especially in the heart. The surface of section shows minute fat 
droplets, and the knife used is oil-stained. 

(b) Microscopy. Primarily the fat is deposited in small gran- 
ules, which have a tendency to run together to form large rounded 
droplets, possessing a light center and a dark contour, or vice versa, 
depending on the manner of focusing. The protoplasm and nucleus 
are pushed to one side. The latter retains its structure and can be 
seen distinctly unless covered by the fat-droplet. In fatty degen- 
eration the tendency of the fat-granules to run together is excep- 
tional. 

Fatty infiltration may be selective, affecting particular parts 
of an organ. In the heart, for instance, it is found in the connective 
tissue between the muscle fibers, and beneath the pericardium. In 




12 NOTES ON PATHOLOGY. 

the liver it is especially marked toward the periphery of the acini, 
where the portal vein deposits the fat coming from the digestive tract. 
Chemically, the fat of fatty infiltration is the same as that 
found in the body normally, namely, a mixture of the neutral fats, 
stearin, palmatin, and olein. 

In the horse olein predominates, the fat therefore is soft and 
yellow ; in cattle the harder and whiter stearin is chiefly found. 

After death, and in certain pathologic states, 
such as gangrene and other degenerations, dur- 
ing life, the fat may take on a crystalline form, 
the crystals being needle-shaped, the so-called 
margaric-acid crystals, or in large rhombic 
ia) choiesterin, {b) Fat- plates, each with a corner cut out, constituting 
CryS, 1;J;L C cr 0U ° d the cholesterin-plates. 

Clinical Causes. — I. Heredity. This is the important factor 
in general obesity. 

2. Disturbed digestion. This may cause chemical changes 
favoring the deposit of fat ; generally, however, it is associated with 
an excessive appetite. 

3. Lack of exej-cise. Not only does deficient physical exercise 
conduce to fatty infiltration, but also lessened mental activity, as is 
seen in certain forms of insanity. In fattening animals it is cus- 
tomary to restrict their exercise to the lowest limit by confinement. 

4. Anemia, probably by lessening oxidation-processes. We 
may have an extensive deposit of fat in chlorosis. The fattening 
of animals for slaughter may be hastened by one or two bleedings. 

5. Alcohol. The ingestion of alcohol, especially in the form of 
malt-liquors, favors the deposit of fat either by increasing the 
consumption of food or by diminishing oxidation. 

6. Local disturbances of circulation interfering with the proper 
nutrition of a part. 

CALCAREOUS INFILTRATION OR CALCIFICATION. 

Calcification is the deposition in the tissues of earthy salts, 
principally the carbonates and phosphates ot calcium and mag- 
nesium. 

Physiologic example. The deposit of salts in bone. The 
salts of pathologic calcification do not differ from those deposited 
in health. 



CALCAREOUS INFILTRATION OR CALCIFICATION. 13 

The term ossification should never be used as synonymous 
with calcification. Calcification is only a step in the process of 
ossification. 

Pathologic Seats] 1. The tissues that normally tend to undergo 
calcification, as cartilage. 

2. The connective tissues in general, particularly those ot the 
blood-vessels. 

3. Tumors. 

4. Foreign bodies, as dead parasites {Trichina Spiralis). 

5. Old inflammatory foci. 

6. Thrombi and emboli, especially in veins (Phleboliths). 

7. Ganglion cells of the nervous system and epithelial cells. 

8. Certain cavities, as that of the gall-bladder, of the urinary 
bladder, and of the intestines. The deposits here take the form 
of concretions or stones, the composition of which varies. They 
are as a rule not made up of earthy salts. 

True calcification affects tissues the blood supply of which is 
poor. Cartilage, for example, possesses no capillaries, and its cells 
are separated very widely from one another. 

Morbid Physiology. — (a) There may be an excess of earthy 
salts in the blood, a condition present in osteomalacia. The salts 
are removed from the bones and deposited in other tissues. (Meta- 
static calcification.) 

(b) In other cases the calcification can only be explained by 
ascribing it to defective nutrition. 

Morbid Anatomy. — We meet calcareous infiltration : 

1. In plates — especially in tissues arranged in layers, as in the 
dura mater, the serous membranes of thorax and abdomen, the 
intima of blood-vessels. 

2. In granules, which may be microscopic in size or larger. 
The organ preserves its outline, the surface of section is gritty. 

3. In spicules and needles, as in the brain, extending in various 
directions, especially near the surface of the organ. 

Microscopy. Both the cells and the intercellular substance are 
affected. In connective tissue, the intercellular substance, in epi- 
thelium, the cells are first affected. The cell-body becomes granular ; 
the nucleus is concealed by the granules and remains unstained. If 
the process is intense, the cells appear black and their outline is 
obscured. 



14 NOTES ON PATHOLOGY. 

There is in some pathologic processes an attempt at ossifica- 
tion, but the new bone is imperfect. 

It differs from normal bone in several ways. 

i. The cells are not arranged in whirls around a central vessel. 

2. There is no formation of regular plates around canals. 

3. The intercellular substance is stained by hematoxylin, 
while that of normal bone is not. 

Reactions and Tests. The mineral acids dissolve the granules 
with effervescence and the liberation of C0 2 . The granules are 
insoluble in ether and in alcohol, and are thereby distinguished 
from fat-granules. 

Clinical Causes. — 1. Osteomalacia and other diseases break- 
ing down bony tissue. 

2. Old age. Here the circulatory system is especially selected 
by the infiltration. 

3. Defective circulation. 

4. Poisons, especially corrosive sublimate. The manner in 
which poisons produce calcification is not well understood. They 
may cause anemia of the tissues. In HgCl 2 poisoning, the deposit 
occurs especially in the renal epithelium. Bismuth and aloin act 
similarly. 

5. In cavities, from a chemical change in the fluids whereby 
the salts are precipitated from solution. 

In gout, sodium urate and also the carbonate and phosphate 
are deposited, this deposit occurring almost exclusively in the con- 
nective tissues, especially that of joints and tendons (Tophi). 

The deposit occurs in the form of fine granules in the cells and 
the intercellular substance. As the disease progresses large masses 
or minute needles may be produced, the latter having the peculiarity 
that they run parallel with the fibers of the tendons. The urate 
salts are soluble in mineral acids, with the production of crystals of 
uric acid. 

PIGMENTARY INFILTRATION. 

This consists in the deposit of abnormal quantities of pigment 
in the tissues. 

Normal seats. The red blood-corpuscles, the skin, the choroid 
coat of the eye, the hair, etc. 

Morbid Physiology.— The pigment may be introduced 
from without, external, or may be formed within the body, internal 



PIGMENTARY INFILTRATION. 15 

pigmentation. The latter is again divided into (a) hematogenous and 
(b) metabolic pigments. Hematogenous pigments are those derived 
from the coloring matter of the blood ; they are either hemoglobin 
or derivatives of it. The metabolic pigment is elaborated out of 
the albuminates of the cells themselves ; or it may be brought to 
the pigmented parts by wandering connective tissue cells. 

The pigment of the rete mucosum is of metabolic origin. ' 

Hematogenous Pigmentation.— The hematogenous pig- 
ments are hemoglobin, hemosiderin, hematoidin, biliary pigment, and 
ferrous sulphid. The pigmentation occurs in one of two ways : 

(a) The pigment may stain the tissues in a soluble form, in 
other words, it may be hemoglobin. The first tissue to be stained 
is the blood — hemoglobinemia. In severe degrees of this condition, 
the hemoglobin also colors the urine — hemoglobinuria. Hemoglo- 
binemia is met with in some of the infectious diseases, as pyemia, 
and in malaria; after the injection of certain poisons; sometimes 
after the transfusion of serum from one animal to another. 

(b) The pigment may be deposited in an insoluble form, being 
a decomposition-product of hemoglobin. The insoluble pigments 
are hemosiderin — a dark, granular pigment, containing iron — and 
hematoidin, a brownish pigment, occurring in rhombic crystals, 
not containing iron. The form which the insoluble pigment takes 
depends to some extent upon the activity of the tissues the seat 
of pigmentation. Where active cell-processes are going on, hemo- 
siderin is produced ; where this is not the case, hematoidin will be 
formed. In old hemorrhagic foci in the brain, we find hemosiderin 
at the periphery, hematoidin in the center. 

Melanosis is a general tendency to the formation of abnormal 
blood-pigments, which appear as minute granules in the blood itself 
or in organs. It occurs chiefly in malaria, where the pigment may 
be so abundant, particularly in the pernicious varieties of the fever, 
as to cause capillary emboli. These are met with especially in the 
brain. The pigment of melanosis may be devoid of iron ; it then 
resembles melanin ; sometimes it contains iron. The malarial 
pigment is generally free from iron. 

Note. — The student should observe that the term melanosis has nothing to do 
with the metabolic pigment melanin ; it signifies the deposition of altered blood-pigment. 
The word originated at a time when the differentiation of the various pigments had as yet 
not been attempted. 



1 6 NOTES ON PATHOLOGY. 

Morbid Anatomy. — We find the insoluble pigments in 
bruises — here chiefly as hemosiderin — and in hemorrhages in the 
interior of organs. In the latter instance the pigment is apt to 
remain for a long time, assuming often a bluish or slate color, as in 
the intestines after an attack of dysentery. 

Tests for blood-pigment. To a watery solution of the blood- 
stain add tincture of guaiac; a white or whitish-red precipitate 
is produced which turns blue on the addition of an ethereal solu- 
tion of hydrogen dioxid. The blue precipitate may be dissolved 
out with alcohol. (A/men's Test.) This test is very characteristic. 

The spectroscopic test, which is absolutely positive. The 
spectrum of hemoglobin (i. e. oxy-hemoglobin), consists of two dark 
bands, one at the junction of the yellow and green, the other in the 
middle of the green. Non-oxidized hemoglobin presents a single 
band, which may be considered to be the result of the union of the 
two oxy-hemoglobin bands. It is, however, smaller than the com- 
bined width of these two bands. Methemoglobin gives rise to 
three dark bands, the two characteristic of oxy-hemoglobin, with 
an additional one in the orange. 

Bile-pigmentation : Jaundice , or Icterus. Since bile is elaborated 
exclusively by the liver, the origin of jaundice must always be 
hepatogenous. It may, however, arise in one of two ways : (a) 
from simple obstruction of the bile-ducts ; (J?) from excessive forma- 
tion of bile-pigment, this generally occurring when there is an ex- 
aggerated destruction of blood-coloring matter. It is the latter form 
to which some clinicians give the name of hematogenous jaundice. 

Tests. Bile-pigment is insoluble in water and in alcohol ; it is 
soluble in chloroform, and gives a pretty play of color with nitrous 
acid or nitric acid containing nitrous acid fumes. {Gmelin-Heintz' 
Test) 

Ferrous sulphid, FeS. This results from the action of hydrogen 
sulphid on the iron contained in the hemoglobin. It is seen post- 
mortem in the abdominal walls and peritoneum, as a diffuse bluish 
discoloration. 

Metabolic Pigmentation.— The pigment— called melanin 
— is elaborated out of the protoplasm of the cells, without the 
intervention of blood-pigment. It occurs normally in the skin^ 
the choroid, in hair, etc. Its composition is variable — sometimes it 
contains iron, at others it does not. Sulphur is generally present. 



SEROUS INFILTRATION. DROPSY. 17 

Pathologic occurrences, (a) Addison's disease. The chief char- 
acteristic of this is the bronzing of the skin, due to an excessive 
deposit of melanin. The majority of cases are associated with dis- 
ease of the suprarenal capsules. 

(5) Tumors — as melanotic sarcoma, or melanoma. 

(c) In degenerations of muscles, as in the heart, particularly 
in atrophy. 

Tests. Melanin is as a rule soluble in boiling acids, and in 
boiling KOH ; also in boiling alcohol. Sometimes it is insoluble. 

■ External Pigments. — I. Bacterial pigments— as in blue 
pus, the color of which is due to the bacillus pyocyaneus. 

2. Silver — which may be deposited during the medicinal ad- 
ministration of silver salts. The pigment discolors the skin, pro- 
ducing the condition termed Argyria. 

3. Coal dust, especially in the lungs — Anthracosis. When the 
pigmentary deposit is excessive, it leads to chronic fibroid changes. 

4. Iron-dust. Siderosis. 

5. Stone-dust. Calcicosis. 

6. Tattoo-pigment. This is found also in the lymphatic glands 
nearest to the tattooed area. 

7. Lead. The blue line on the gums. 

SEROUS INFILTRATION. DROPSY. 

This consists in the infiltration of the tissues with diluted lymph. 

Pathologic seats. (1) Serous cavities. (2) Loose areolar connec- 
tive tissue. (3) Lungs. (4) Epithelium — here it is probably of a 
different character, resembling more a degeneration. 

Morbid Physiology. Serous infiltration may be brought 
about in various ways. (1) Through obstruction of the lymphatics 
and veins. Being the result of mechanical influences, the dropsy 
under these conditions appears first in the dependent parts, as in 
the lower limb, and in the lower portions of the pleural and peritoneal 
cavities. (2) Through a change in the composition of the blood, as 
in anemia. Weakness of the vessel-walls may contribute to the 
production of the infiltration. (3) Through changes in metabolism. 
The healthy state of the organism depends upon the normal char- 
acter of the interchange constantly going on between the tissues 
and the blood. This interchange is not merely the result of a 
mechanical transudation ; it is an active process. If disturbed at 



j 8 NOTES ON PATHOLOGY. 

any point, disease develops, at one time serous infiltration, at 
another, as we shall see later, inflammation. (4) Through changes 
in the walls of the blood-vessels : {a) over-distension (b) disease 
of the vessel-walls. 

Character of the Fluid. It has the same composition as the 
lymph, but contains more water and less corpuscular elements. 
From inflammatory fluid, which it resembles, it is distinguished by 
being less inspissated. Its specific gravity does not exceed 1016, 
and its proportion of albumin is less than three per-cent. Inflam- 
matory fluid is denser and contains more albumin. 

Morbid Anatomy — (a) Macroscopy. The part, as a limb, is 
swollen, pale, somewhat translucent in appearance, pits on pressure, 
and has a lower temperature than the same part in health. In the 
case of the lung, we find that the organ is enlarged and on section 
oozes a frothy serum. 

Different terms are employed, according to the seat of the 
effusion : 

1. Anasarca. When the general subcutaneous connective 
tissue is infiltrated. 

2. Edema is applied to the infiltration of the subcutaneous 
tissues and the internal organs, as edema of the lungs. Edema ot 
the brain is in reality edema of the membranes, the pia-arachnoid. 

3. Hydropericardium, hydrothorax, and ascites refer to serous 
effusion into the pericardial, pleural, and abdominal cavities respec- 
tively. 

(b) Microscopy. The fluid infiltrates the intercellular substance 
and separates the cells widely from each other ; the fibrils of the 
intercellular substance are swollen and also widely separated. These 
features are seen best in fresh tissues. 

In epithelium the process is really a degeneration ; it occurs 
principally in catarrhal and other inflammations of mucous mem- 
branes ; it is also observed in the muscle of the heart. In the case 
of mucous membranes the cells are large and filled with fluid ; they 
lose their shape and appear dropsical. Clear vacuoles, free from 
the granules found in the protoplasm, are present. In the heart the 
serous degeneration gives rise to the semblance of cavities within 
the muscular fibers. 

Clinical Causes. — 1. Valvular Heart Disease. The dropsy 
begins in the feet. 



GLYCOGENIC INFILTRATION. 19 

2. Diseases of the liver ; especially cirrhosis, which causes ob- 
struction of the portal circulation, and this in turn ascites. 

3. Diseases of the kidney. Here several factors are active in 
the production of the serous infiltration — (a) changes in metabolism, 
(b) changes in the composition of the blood, and (c) changes in the 
walls of the blood-vessels. The edema begins, as a rule, in the loose 
areolar tissue of the eyelids. It may be noticed quite early in the 
finger-tips, from the swinging of the hands in walking. 

4. Cachectic states, as in tuberculosis and cancer. The edema 
in cachexia depends upon changes in the composition of the blood 
and upon a feeble state of the heart. 

5. Nervous disturbances , as in hysteria and in certain organic 
diseases of the nervous system. In the former, the edema is brought 
about by changes in metabolism, the result of trophic disturbances. 

GLYCOGENIC INFILTRATION. 

This is the deposit of glycogen in the tissues. 

It is normal in the liver. 

Under pathologic conditions we find it (a) in pus, (b) in several 
organs in diabetes, chiefly in the kidney, and (c) in certain tumors. 
The process lies on the border-line between infiltrations and degen- 
erations, for there is a tendency to the disintegration of the affected 
cells. 

The deposit appears as minute droplets in the cells, especially 
about the nucleus. The droplets resemble somewhat those of fat. 

Test. Glycogen strikes a dark reddish-brown color with iodin, 
which should be distinguished from the yellowish-brown color 
which that reagent imparts to normal tissues. The test is applied 
as follows : 

The section is for a moment immersed in a solution of 

Tincture of iodin 1 part. 

Absolute alcohol 4 parts. 

It is then washed in water and mounted in glycerin. 

DEGENERATIONS. 

The degenerations are amyloid, hyaline, mucoid, colloid, paren- 
chymatous (cloudy swelling), and fatty. 



20 



NOTES ON PATHOLOGY. 



AMYLOID DEGENERATION. 
This is a progressive degenerative process, affecting especially 
the connective tissues, and giving rise to the formation of a sub- 
stance characterized by the amyloid reaction. 

It is not found in health, although it occurs at times in organs 
belonging to apparently healthy individuals — it is there indicative of 
local disease. 

Seats. Liver, kidney, spleen, walls of the intestines and 
heart, nervous system and prostate gland. The first three of 
these are affected with equal frequency, and more often than the 
other organs. 

Morbid Physiology. — Amyloid substance is the result of 
a reaction occurring between something derived from the blood and 
the juices of the tissues. It does not exist preformed in the blood, 
therefore its deposit is not an infiltration. The ultimate cause of 
its formation is perhaps in many cases, but not in all, the loss of 
potassium salts. 

The amyloid material is an albuminoid. It contains less potas- 
sium and phosphoric acid and more sodium and chlorin than nor- 
mal tissue. Alkalies and acids do not dissolve it, and it is very 
resistent to peptic digestion and to putrefactive processes. 

Morbid Anatomy.— (a) Macroscopy. The affected organ 
is larger than normal, the increase in size being at times remarkable, 

the outline is uniform, the borders, if the 
organ have any, are rounded, the sub- 
stance of the organ is denser, i. e., less 
friable, the elasticity is decreased — the 
organ may be doughy and may pit on 
pressure. The surface of section is paler 
than normal, and is somewhat translu- 
cent at the edges. The appearance is 
well described by the term " waxy " or 
" bacony." As a rule the organ is affected 
uniformly. Not rarely, however, the process is circumscribed to 
minute areas ; indeed, it may not be apparent to the naked eye at 
all, unless the characteristic test is applied. 

It is particularly in the spleen and kidney that the degeneration 
shows a tendency to limitation. In the former it selects the lym- 
phoid bodies and adjacent blood-vessels, the condition produced 




Amyloid degeneration in kidney. 



AMYLOID DEGENERATION. 21 

having received the name of " sago-spleen," from the resemblance 
of these bodies when affected by amyloid disease to boiled sago- 
grains. In the kidney the degeneration may be confined to the 
blood-vessels of the glomeruli. Both spleen and kidney may be 
uniformly affected. 

(b) Microscopy. The microscopic appearance is that of a 
grayish-white, somewhat translucent substance, cloudy in color and 
in shape, and apparently made up of flakes. The nuclei are absent. 
The process begins in the connective tissue of the walls of the blood- 
vessels, and affects both the cells and the intercellular substance. 
From the blood-vessels the process may spread to the surrounding 
connective tissue, and thence to the parenchyma. It is highly 
probable that the parenchymatous tissues undergo primarily fatty 
degeneration, and become subsequently invaded by the amyloid 
material. 

Reactions. 1. Iodin produces a dark reddish-brown color. 
It serves both a naked-eye and as a microscopic test. For the 
former a fresh section should be made, the surface washed 
with water, and LugoPs solution poured on. The reddish-brown 
color of the affected areas contrasts strongly with the yellowish 
or greenish-brown tint which the iodin gives to the healthy 
portions. 

For the microscopic application of the test, the following 
solution is employed : 

5 per-cent watery solution potassium iodid. 
Iodin to saturation. 

A few drops of this solution are added to a watch-glassful of 
water. The section is immersed in the mixture, which should be of 
a sherry- wine color, for one to two minutes ; it is then washed in 
water and cleared in glycerin. 

2. Gentian-violet produces a light red color with the amyloid 
substance, while the unaffected tissues become blue. The test 
is only used for microscopic differentiation. It is applied as 
follows : 

(i.) Place the section for one to two minutes in a five per-cent 
watery solution of gentian-violet. 

(2.) Wash in water acidulated with acetic acid — two or three 
drops to a considerable quantity of water. 

(3.) Examine in this solution or in water. 



22 NOTES ON PATHOLOGY. 

The gentian-violet reaction is also given by levulose, while 
cholesterin and glycogen respond to the iodin-test. 

The amyloid reaction consists in the development of a blue 
color when iodin and sulphuric acid are applied to amyloid sub- 
stance. It is not always obtained, nor is it important. The failure 
to get it in all cases suggests the possibility that the amyloid 
substance is not always of the same composition, but that there is 
a series of related degenerations leading up to amyloid. 

The starch reaction is most frequently given by the amyloid 
bodies. 

Clinical Causes. — Chronic suppuration, especially that 
dependent upon tuberculous or syphilitic bone-disease. 

Amyloid Bodies. — These are small masses of concentrically 
arranged amyloid material, which are found in the prostate gland and 
in the nervous system. The change is here not progressive. The 
bodies involve the epithelium rather than the connective tissue — at 
least in the prostate glands, where the epithelial lining of the follicles is 
affected. They may occur in healthy prostate glands, but are most 
common in the prostates of old persons in whom the organ is 
hypertrophied, and its follicles are in a state of catarrhal inflam- 
mation. In the prostrate gland the bodies are visible to the naked 
eye, and frequently contain pigment ("grains of snuff"). In the 
nervous system they are microscopic in size, and are found beneath 
the ependyma of the cavities. Though met with in healthy brains 
and cords, they are most abundant in sclerotic conditions and in 
epilepsy. 

They give the iodin-reaction. 

HYALINE DEGENERATION. 

This consists in the formation of a substance similar in appear- 
ance and composition to amyloid material, but not presenting the 
reactions peculiar to the latter. It attacks almost exclusively the 
connective tissue, particularly of the walls of the blood-vessels, and 
shows no tendency to spread to surrounding tissues. 

The organs in the vessels of which it is most common, are the 
brain, the lymph-glands, the kidney, the heart, and the ovary. 




MUCOID OR MYXOMATOUS DEGENERATION. 23 

Morbid Physiology.— Very little is known of the morbid 
physiology of hyaline degeneration. Its formation is supposed to 
be analogous to that of amyloid substance, 
i. e. } the result of a reaction between an ele- 
ment exuded from the blood-vessels and the 
juices of the tissues. The conglutination of 
the blood-plaques in the clotting of blood 
within the blood-vessels is a form of hyaline 
degeneration. 

It is possible that the falling of blood- 
plaques against the walls of the vessels may 
constitute the starting point of hyaline de- 
generation just outside of the endothelium. 

Morbid Anatomy. — The substance HyJiTO a t^!^. arou,ld 
appears as minute, irregular, glassy masses 

just outside of the endothelium of the small vessels and capillaries, 
giving to them a beaded appearance. In the larger blood-vessels 
it affects the walls more uniformly — the intima and the connective 
tissue of media. This is particularly the case in the ovaries of old 
women. Exceptionally, the process extends to the neighboring 
connective tissue and to the parenchyma. Probably the paren- 
chyma is first removed through other degenerations, and then 
replaced by hyaline material. We find these extensive areas of 
hyaline substance in chronic fibroid inflammations, especially in the 
heart, where the areas may be visible to the naked eye. 

Clinical Causes. — /. Acute infectious diseases. In these the 
process affects especially the capillaries. 

2. Old age : in the walls of the blood-vessels. 

3. Chronic inflammations , as in the heart and in the blood- 
vessels in sclerosis. 

4. Tumors: cylindromata. 

MUCOID OR MYXOMATOUS DEGENERATION. 

This consists in the formation of a colorless, viscid substance, 
containing mucin. 

Normal examples. 1. In epithelium. The columnar epithelial 
cells of mucous membranes form mucin {goblet-cells}. 

2. In connective tissues, as in the jelly of Wharton of the 
umbilical cord, and in the vitreous humor of the eye. 



24 NOTES ON PATHOLOGY. 

Pathologic seats, i. Mucous membranes. 

2. Epithelial and connective tissue tumors. 

3. In certain processes of softening. 

Morbid Physiology. — Nothing definite is known of the 
way in which the mucous material is produced. 

Morbid Anatomy. — (a) In epithelium — the mucous dis- 
charge of catarrhal inflammation. This is a viscid, ropy, transparent, 
colorless substance containing mucin. 

Microscopically, we find that the epithelial cells are larger than 
normal, and that they present a granular periphery and a shining 
center. The mucin-granules may be discharged, the cell remaining 
attached, or the degenerated cells themselves may be thrown off in 
large numbers. We find in addition, evidences of karyokinetic pro- 
cesses in the epithelial cells, and here and there also newly formed 
cells not perfectly developed. The appearances we find in mucous 
membranes are also met with in cavities lined by epithelium, i. e. y 
in cysts. 

(b) In connective tissue the intercellular substance is especially 
involved, the fibrils being swollen, transparent, and obscured in 
outline. The material produced is stringy, gelatinous, and color- 
less. The connective tissue cells are generally normal and readily 
take the stains, but on account of pressure assume modified forms, 
being frequently stellate or spindle-shaped. They may eventually 
undergo fatty or mucoid change. Mucoid degeneration of con- 
nective tissue is common in bone, cartilage, fat, and in many con- 
nective tissue tumors. In epithelial tissue, as we have seen, the 
degeneration affects principally the cells, in connective tissue, the 
intercellular substance. 

Reactions. 1. Mucin is insoluble in water, but swells in it. 

2. It is precipitated in stringy, ropy masses by alcohol and by 
acetic acid. Under the microscope these reagents give rise to a 
cloudy or granular appearance. The affected epithelial cells become 
turbid. This reaction distinguishes the mucoid substance from 
dropsy of the cells and from pseudomucin. 

3. It is not precipitated by boiling or by tannin. 

Clinical Causes. — 1. Catarrhal inflammations of mucous 
membranes. 

2. Large cysts lined by epithelium, as those of the ovary. 



COLLOID DEGENERATION. 25 

3. Many so-called colloid cancers, in which the epithelial cells 
are the seat of mucoid, and not a colloid, change. 

4. Myxomatous connective tissue tumors. 

5. Certain processes of softening of bone and cartilage. 

COLLOID DEGENERATION. 

This is the conversion of the protoplasm of epithelial cells into 
a gelatinous material resembling mucin, but not giving its reactions. 

Normal seat. The epithelium of the thyroid gland. 

Pathologic seat. It occurs only in epithelial structures and 
affects exclusively the cells. 

Morbid Physiology. — Of its mode of formation nothing is 
known. 

Morbid Anatomy. — (a) Macroscopy. The affected organ is 
enlarged, the amber-colored, gelatinous, colloid substance being 
distributed in " nests " or follicles, whereby a peculiar appearance, 
resembling somewhat that of a honey-comb, is produced. 

(J?) Microscopy. The colloid material occurs in the form of 
droplets in the protoplasm of the cells. These droplets display, as 
a rule, no tendency to run together, but grow in size at the expense 
of the cells, which may become entirely colloid. When this point 
is reached, the cells drop into the cavity of the follicle. Frequently 
a concentric arrangement is visible in the colloid substance. It 
seems that nearly an entire row of epithelial cells becomes colloid, 
is cast off, and forms a ring in the center of the follicle ; a second 
row of cells has a like fate, and so on until several concentric 
layers are produced. There is no sharp line of separation between 
the rings, only a slight difference in color and a few pigment- 
granules serving to demarcate them. 

Reactions and Stains. Colloid material does not swell in water 
and is not precipitated by alcohol, acetic acid, or chromic acid. 

It is stained best by a fluid composed of acid-fuchsin and picric 
acid. This imparts to it a reddish-orange color, which is a mix- 
ture of the colors of the two stains . The other tissues present the 
yellow tint of the picric acid. 

Clinical Causes. — I. Thyroid hyperplasias and epithelial 
tumors of the thyroid gland. 

2. True colloid cancers , as those of the pylorus. 



26 



NOTES ON PATHOLOGY. 



3. Renal cysts. 

4. Renal tube-casts. 

The renal epithelium has a pronounced tendency to undergo 
colloid change. It ranks next to the thyroid in frequency as a seat 
of the degeneration. 



PARENCHYMATOUS OR ALBUMINOUS DEGENERA- 
TION, OR CLOUDY SWELLING. 

This is a change whereby the soluble albuminous substances of 
the cells are precipitated in an insoluble form, as minute granules. 
Seats. Archiblastic tissues. 

Morbid Physiology. — Cloudy swelling is the first step 
toward degeneration. The granules are readily soluble, hence the 
change bringing about their precipitation is not a profound one. 
The process, indeed, may lie within the limits of normal physiology, 
for under certain conditions of stimulation, still physiologic, the 
epithelial cells, particularly those of the liver and kidney, become 
cloudy, from the presence of an excess of proteid-granules. These 
subsequently disappear with the re-establishment of the nutritive 
equilibrium. Under other circumstances the process is pathologic, 
and is the precursor of further degenerative changes. 

Morbid Anatomy. — (a) Macroscopy. If the change is 
slight no alteration is noticeable. In well- 
marked cases the organ is enlarged and 
its tissue softer, although from being 
swollen within a tense, non-yielding cap- 
sule, it may convey a sensation of in- 
creased consistency. The organ contains 
less blood, and on section is paler than 
normal ; its structure is obscured, the 
normal translucency is lost, and the organ 

Cloudy swelling of the kidney. 1 1 •{• • . 1 j , . , 

looks as if it had been cooked. 
(b) Microscopy. The cells are larger and more rounded ; they 
have lost their sharp outline, and are cloudy from the presence of 
innumerable fine granules. The nuclei are not well stained; in 
advanced cases they may not be apparent. The protoplasm may 
be broken down into a granular detritus; or there may be fatty 
degeneration. 




FATTY DEGENERATION. 27 

Some cells have a greater tendency to break down than others, 
e. g., the renal epithelium. The granular debris resulting from the 
degeneration of the renal cells combines with an albuminous sub- 
stance to form tube-casts. 

Reactions. 1. The granules are dissolved by acetic acid. Fat- 
granules which often are similar in appearance are not dissolved, 
but become more distinct under the action of acetic acid. 

2. The granules are insoluble in alcohol, in ether, and in 
chloroform — fat-granules are dissolved by these reagents. 

3. Being albuminous, the granules give the proteid-reactions. 
Cloudy swelling, like all other degenerations, is best studied in 

fresh tissue. 

Clinical Causes. — I. Fevers. Heat alone suffices to pro- 
duce cloudy swelling. 

2. Acute infectious diseases. The cloudy swelling may be due 
to the fever or to the action of a toxin. Some of the infections 
have a predilection for certain organs ; as, for instance, diphtheria 
and yellow fever, which produce cloudy swelling especially in the 
kidney. They do this even in the absence of fever, particularly 
diphtheria. 

3. Poisons. Non-bacterial. 

(a) Alcohol. This, even in small quantities, produces cloudy 
swelling, probably on account of a stimulation of the cells to take 
up an excess of albuminous material. Large doses cause a more 
permanent degeneration. 

(b) Phosphorus, arsenic, mercuric chlorid. The last may lead 
very rapidly to cloudy swelling. 

(c) Chloroform and ether. Here the cloudy swelling may be 
due to an attempt at elimination of the poison. 

FATTY DEGENERATION. 

This is a disintegrating process whereby the proteids of the 
tissues are converted into fat. 

Normal example. The formation of milk. Really both pro- 
cesses, fatty infiltration and fatty degeneration, take part in the pro- 
duction of milk. 

Pathologic seats. It may occur in all tissues, more especially, 
however, in the liver, kidney, walls of blood-vessels, and muscular 



2% NOTES ON PATHOLOGY. 

substance of the heart. In these localities it constitutes almost a 
distinct disease. 

It is also found in all morbid processes where destroyed cells 
are to be eliminated. 

Morbid Physiology.— Deficient supply of oxygen is the 
basis of the process. The diminution in oxygen interferes with the 
combustion of the fats and of the proteids ; the latter, not being 
oxidized into urea, water, C0 2 , etc., show a tendency to be con- 
verted into fat. 

The most frequent causes of deficient oxidation are : 

1. Diminished blood supply — the most common of all causes. 

2. Fever, which impairs the oxygen carrying-power of the 
hemoglobin. 

3. Poisons. Their mode of action is obscure, but they probably 
diminish oxidation. 

Morbid Anatomy. — (a) Macroscopy. The organ may in 
/^v >^ *^ e early stages be slightly augmented in size ; later 
^Sm \§lt it is small and atrophied. It is paler in color and 
degenStion. somewhat yellowish, either uniformly so or, as in the 
heart, in streaks. Its specific gravity is lighter ; the 
consistency is diminished. On the surface of section 
\b) Fatt^ 37 fat-drops are seen, and the section-knife may be oil- 
infiitration. stained. 
(b) Microscopy. The cells are more spherical and contain fat- 
granules, some very minute, others larger and shiny ; rarely small 
droplets are present The granules may completely fill the cells. 
The nucleus at first is only concealed, but later it also becomes 
degenerated. Eventually the cell breaks down into a fatty detritus. 
In the early stages the granules are not readily distinguished 
from those of cloudy swelling, but as a rule they are larger and 
more refracting. In some situations the fat-granules show a 
tendency to fuse and form distinct droplets, as in fatty infiltration. 
This occurs particularly in the liver, in acute cases of fatty degen- 
eration, and in the nervous system. 

In fatty degeneration of muscles the fat-granules appear in 
rows running parallel with the long axis of the fibers, but without 
any special connection with the nucleus. 

Compound granule-cell. This is a large cell made up of fat- 
granules. It is either an epithelial cell that has undergone fatty 



FATTY DEGENERATION. 29 

degeneration, or a wandering connective tissue cell that has taken 
up much fatty detritus. The latter variety is very common in the 
nervous system. 

After death the fat is apt to assume the crystalline forms pre- 
viously described, viz., needles of margaric acid and plates of choles- 
terin. The latter are also formed during life. The fats are the 
glycerites of oleic, palmitic, and stearic acid. 

Reactions. 1 . The fat-granules are insoluble in acetic acid and 
in the alkalies. 

2. They are soluble in ether, in chloroform, and, slowly, in 
alcohol. 

3. They are stained black by osmic acid. A ready method 
giving fairly good results is to cut the sections with a freezing- 
microtome, and immerse them in a one-half per-cent solution of 
osmic acid for one-half to one minute ; then wash and examine in 
water. As tissues preserved in alcohol frequently fail to show fatty 
degeneration, it is best to harden them in a mixture composed of 
three parts of Miiller's fluid and one part of a one per-cent solution 
of osmic acid. The specimen is left in this, in the dark, for two 
weeks, and is then washed in running water for twenty-four hours, 
to remove the excess of osmic acid. It is subsequently hardened 
in alcohol, imbedded in celloidin, and cut into sections. 

Alcohol does not dissolve the fat acted on by osmic acid, but 
both xylol and chloroform do. In mounting the section, pure 
balsam — not xylol-balsam — should be used. 

Clinical Causes. — I. Old age. The degeneration may be 
found in all organs, but affects especially the blood-vessels. 

2. Anemia, (a) Acute anemia, as that due to hemorrhage. 
The fatty degeneration may be very rapid, particularly in the heart 
and in the posterior layer of the retina. The degeneration in the 
latter case results in blindness, (b) Chronic anemia — both the 
essential forms, leukemia, chlorosis, progressive pernicious anemia, 
and the symptomatic — as those from cancer and tuberculosis. The 
fatty degeneration caused by these may be general. 

3. Local anemia. In an hypertrophied heart fatty degenera- 
tion is very common on account of an insufficient blood supply. 

4. Fevers. These cause defective oxidation. 

5. Poisons, (a) Toxins, as in yellow fever, in which the liver is 
frequently affected. (b) Non-bacterial poisons, as carbon monoxid, 
phosphorus, chloroform, iodoform, etc. 



CHAPTER II. 



NECROSIS. 



Necrosis is the change that cells undergo when they die in the 
midst of living tissue. Two forms are described : 

(a) Necrosis proper ; true, or direct necrosis. This is the death 
of a large number of cells, the dead mass being separated by a 
distinct line from the living tissues. 

(b) Necrobiosis, or indirect necrosis. This is the gradual death 
of cells in irregular areas. There is no line of separation between 
the dead and the living tissues. 

The degenerations previously considered are forms of necro- 
biosis. In this chapter we shall only deal with true necrosis. 

Causes of Necrosis. — 1. Destructive agencies, including 
micro-organisms. 

2. Disturbances of circulation. 

3. Disturbances of innervation. 

About all necrotic tissues there exists an area of reaction, 
known as the line of demarcation. It is the seat of active inflam- 
matory processes, and has for its object either the removal of the 
dead part or the building up of new tissue. The former end is 
achieved by liquefaction and softening processes ; the latter by the 
process of organization. 

The changes taking place about a necrotic focus are largely 
under the control of the nervous system. But even before the 
nervous functions come into play, there is an immediate and direct 
reaction, due to the influence of the dead cells upon the living. It 
manifests itself in a rapid accumulation of round cells about the 
destroyed areas. 

The force or cause which brings about this peculiar phenome- 
non is not clearly understood — it has been named positive chemo- 
taxis. We may define this as the attractive force which dead tissues 
exert upon living cells. 

(30) 



COAGULATION NECROSIS. 31 

Fate of the necrotic tissue. 1 . It may be absorbed \ either in the 
form of a fluid, or in the form of a granular debris. In the latter 
case there is also a certain amount of fluid to aid in the absorptive 
process. Absorption occurs principally in the interior of organs. 

2. It may be retained. The dead part may become surrounded 
by a connective tissue capsule — encapsulation. The mass may then 
become calcified or the dead tissue may be converted into a fluid, 
in which case it constitutes a cyst (softening-cyst). 

3. It may be thrown off. 

(a) In the form of a large mass. Here the liquefaction takes 
place along the line of demarcation until the part is loosened and 
falls off. This is common in the necrosis of bone, the separated 
mass being called a sequestrum. 

Sphacelus is the corresponding term for soft parts. 

(b) In the form of small particles (molecular) or a fluid. 
Example — pus. 

The dead parts may be replaced — (a) By the same tissue as 
that destroyed — regeneration. 

This is not frequent ; it is in inverse ratio to the extent of the 
necrosis and the specialization of the tissue. 

(b) By connective tissue — cicatrization. This is by far the 
more common process. The connective tissue is the product of the 
line of demarcation. 

The individual cells in the various forms of necrosis to be 
considered, are the seat of the elementary processes of degenera- 
tion, especially fatty degeneration. 

The following are the forms of necrosis : Coagulation, liquefac- 
tion , and cheesy necrosis, and gangrene. 

COAGULATION NECROSIS. 

This is a form of necrosis resulting in the production of fibrin. 

Example. The coagulation of the blood, which will be con- 
sidered under Thrombosis. The process also takes place in the 
tissues. 

Morbid Physiology. The formation of fibrin in the blood 
depends upon a reaction between components of the blood-plasma 
and of the cells; its formation in the tissues is an analogous 
process. As a result of the breaking down of the tissues the 



32 



NOTES ON PATHOLOGY. 



fibrinoplastin and ferment are liberated, while the tissue-juices 
contribute fibrinogen. The resulting fibrin is identical with that 
found in blood. 

Causes, i. Chemical substances, as the mineral acids, mercuric 
chlorid, etc. These most frequently cause coagulation necrosis on 
mucous membranes. 

2. The toxins of micro-organisms, especially that of the bacillus 
of diphtheria. It is not the organism itself that kills the tissues 
and leads to the liberation of fibrin-factors, but the poison which 
it elaborates. 

3. The sudden and total withdrawal of the blood-supply. 

Morbid Anatomy. — {a) Macroscopy. The process appears 
in three distinct localities : in the blood, where the product takes 




Diphtheritic membrane from mucous surface. 

form of the containing vessel, on mucous membranes, and in the 
interior of organs. The first will be discussed under Thrombosis. 

On mucous swfaces coagulation necrosis gives rise to the produc- 
tion of a false membrane. This is whitish-gray or buff-colored 
membrane, varying in consistence, and ranging in thickness from 
the merest filament to a thick layer. From exposure and the 
deposit of foreign matter the color may become dark or almost 
black. 

The membrane may extend deeply into the tissues and be 
firmly adherent, or it may be superficial and removed with ease. 
This depends largely upon the anatomic structure of the parts 
affected. Frequently the membrane is stratified. 



COAGULATION NECROSIS. 33 

In organs the process affects the area of distribution of the artery 
to the stoppage of which it is due, and gives rise to the anemic 
infarct. This is a conical or pyramidal mass, of a pale, grayish, 
yellowish, or reddish color; it projects beyond the surrounding 
tissues, is denser, contains less blood and less fluid, and has a very 
sharp outline. As a rule no blood is present at all ; occasionally 
there may be a little, giving rise to the reddish tint. 

(b) Microscopy. The fibrin appears under different forms — as a 
homogeneous mass, as fine granules, as fibrillar fibrin (as in the 
blood), as a fine network, or as a coarse mesh-work of " lumpy " or 
" knobbed " appearance, or as flakes. The fibrin formation involves 
all the tissues, the intercellular substance, the cells, and the nuclei. 
The latter are affected very early in the process and fail to take 
the stain even before the fibrin has made its appearance ; this is 
the first characteristic feature. No other necrosis attacks the 
nuclei so rapidly; in the anemic infarct it is a question of hours 
only. 

The stratification of membranes is due either to an alternation of 
different forms of fibrin or to the presence of round cells between 
the layers. 

These round cells which separate the membrane into layers 
are either leukocytes that have been spared by the necrosis or are 
wandering cells — leukocytes or connective tissue cells — that have 
migrated into the membrane. Most frequently the layers of fibrin 
are the same. 

When the membrane falls off, it leaves a deep ulcer, except 
in those cases in which it was superficial and confined to the upper 
layers of the epithelium. We may then see no loss of tissue with 
the naked eye, although a certain amount must have been 
destroyed. In the pharynx, tonsils, and soft palate, the necrosis 
extends deeply. In the larynx, on the contrary, it is superficial and 
causes no loss of substance apparent to the naked eye. This fact 
gave rise to the former belief that diphtheria of the pharynx and 
croup of the larynx were two distinct diseases. We now know that 
they are the same. 

Coagulation necrosis is an acute process. The dead part is 
separated by a process of softening, which is brought about by an 
accumulation of leukocytes. These evidently, judging from their 
presence within the membrane, make several unsuccessful attempts 
before they succeed in removing the membrane. 

3 



34 NOTES ON PATHOLOGY. 

Liquefaction necrosis and suppuration may take place. 
Stain. Weigert's stain gives a perfect reaction with fibrin. 
The following solutions are employed : 

No. i, Alcohol (95 per-cent.) 6 parts. 

Anilin oil 1 " 

5 per-cent. watery solution gentian-violet . 43 " 

No. 2, 5 per-cent. solution of potassium iodid. 

Iodin to saturation. 
No. 3, Xylol I part. 

Anilin oil 2 parts. 

The application is as follows : Transfer the section from 80 per- 
cent, alcohol into solution No. 1, and keep in this 1 to 2 minutes; 
wash in water. Place the section upon a glass-slide and dry it with 
absorbent paper, then drop on a little of the iodin solution (No. 2). 
Allow this to act for %-% minute, remove the iodin, and dry the 
section with absorbent paper. Differentiate by dropping solution 
No. 3 upon the section from a pipette ; diy, and again drop on 
solution No. 3, repeating the process until clouds of color are no 
longer given off. The section is then cleared in pure xylol and 
mounted in balsam. The fibrin and any micro-organism present are 
colored blue. 

Clinical Causes.— i. Diphtheria. 

2. Dysentery. 

In coagulation necrosis brought about by micro-organisms, we 
commonly find several varieties of bacteria present. 

3. Irritant poisons — mineral acids, corrosive sublimate, etc. 

4. Embolism of arteries, especially of kidney and spleen. 

LIQUEFACTION NECROSIS. 

In this form the juices of the tissues, instead of producing 
coagulation, cause liquefaction of the cells and the intercellular 
substance. The first visible evidence is generally a swelling of the 
cells : they become dropsical, lose their outline ; the nuclei rapidly 
cease to take the stain, and the cells break down into a fluid. Fre- 
quently the fluid is the result of the liquefaction of the intercellular 
substance, the cells floating in the liquid. 

Clinical Causes.— i. Burns. 

2. Embolism of certain orga?is } especially of the brain (acute 
softening of the brain). 



CHEESY OR CASEOUS NECROSIS. ; 

3. Suppuration. — Pus is the result of the liquefaction necrosis 
of the intercellular substance of the tissues, the cells floating in the 
fluid. 

4. It is the terminal stage of other forms of necrosis. 

CHEESY OR CASEOUS NECROSIS. 

This is a process very similar to coagulation necrosis ; like it 
it is characterized by a coagulation of the cell-body and the inter- 
cellular substance, but without the formation of fibrin. From 
fibrin-formation it differs also in being a slow progressive process, 
while the other is rapid. The substance produced is also drier 
and denser than fibrin. Yet it is possible that coagulation necrosis 
is an early stage of cheesy necrosis. 

There are two forms of cheesy necrosis, the dry and the moist, 
In the dry the difference from fibrin is well marked. The moist 
form is a terminal stage of caseous necrosis, being merely the result 
of fatty degeneration and liquefaction necrosis. 

Morbid Anatomy. — (a) Macroscopy. The affected area (in 
dry cheesy necrosis) is structureless, grayish-white, and denser than 
normal ; it is of the consistency of cheese, and fades gradually into 
the surrounding tissues. The central portions are lighter and more 
fatty ; toward the periphery the appearance is more that of coagula- 
tion necrosis. 

(b) Microscopy. As the process is a progressive one, we find 
the cells in different stages of involvement. In the center of the 
area there is a grayish, cloudy field, granular in appearance, some- 
what pigmented, and without nuclei. As we approach the circum- 
ference, we find nuclei in various stages of degeneration — some 
are stained only half, others only at their edges. A peculiar char- 
acteristic is a marked tendency to the accumulation of nuclei at the 
periphery of the necrotic area (" raked field appearance "). 

The presence of this aggregation of nuclei is not easily ex- 
plained. Perhaps the irritant, before causing necrosis, acts as a 
stimulus to the tissues and brings about a multiplication of cells. 

Occasionally the necrotic process is confined to a single cell, 
and then gives rise to the appearance described as giant-cells. The 
protoplasm of these cells has a peculiar opacity. Their formation 
represents a very early stage of cheesy necrosis. 



36 NOTES ON PATHOLOGY. 

Clinical Cause. — The necrosis may occur anywhere ; in the 
majority of instances it is brought about by the tubercle bacillus. 
It is most common in the lungs, in tuberculosis. 



GANGRENE. 

This is the putrefactive fermentation of dead tissues still 
attached to the living body. There are two forms, the dry and 
the moist. 

(a) Dry Gangrene. — This is brought about through the 
withdrawal of the blood supply and the evaporation of the water 
contained in the affected part. 

Morbid Physiology. — The evaporation is facilitated by the 
removal of the skin. The absence of the blood supply — the essen- 
tial cause — is produced by an arrest of the arterial circulation, either 
through embolism or through disease of the vessel-walls. The 
latter pre-eminently favors the occurrence of dry gangrene, because 
in diseased conditions of the vessels the collateral circulation is not 
readily established. 

Morbid Anatomy. — The part is dark, friable, horny, 
" mummified," smaller than normal, and separated from the healthy 
tissue by a line of demarcation. 

Clinical Causes. — I. Drying of the umbilical cord (normal). 

2. Senile gangrene. We have here a thickening of the arterial 
coats, with coagulation of blood within the vessels. Gangrene 
results when the obstruction is diffuse. 

3. Raynaud's disease. The cause here is probably a disturb- 
ance of the nervous system producing spasm of the arteries. 

4. Frost-bite. This also causes contraction of the blood- 
vessels. 

5. Ergotism. 

(b) Moist Gangrene.— This is as a rule brought about by 
the obstruction of the venous outflow ; the affected part is full of 
water. The circulation having ceased, decomposition sets in. The 
latter is due to the action of saprophytic micro-organisms, which are 
responsible for development of the chemical changes pertaining to 
the process. 



GANGRENE. 37 

Morbid Anatomy. — (a) Macroscopy. The part is swollen, 
soft, and juicy; the color is dark, passing through a series of 
shades, from dark-green or bluish to black, due to changes in the 
blood-pigment. The tissues crepitate on account of the presence 
of gas. The skin is raised in blisters, which are filled with a clear or 
a turbid, greenish fluid. There is also a characteristic odor. 

(p) Microscopy. The nuclei disappear rapidly, and the cells 
break down, some into a granular debris, others, from liquefaction 
necrosis, into a fluid. Blood-pigment is deposited, either as hemosi- 
derin or as hematoidin. Fat-crystals may also be formed. The 
muscle-fibers lose their striation, and the nerve-fibers become 
beaded, the myelin presenting a drop-like appearance. Bones and 
tendons are most resistant. Chemically, moist gangrene is a pro- 
cess of oxidation, the end products being H 2 0, C0 2 , H 2 S, and NH 3 . 
But before these final products are reached, aromatic compounds and 
ptomains, several of them active poisons, are generated. These 
may be absorbed and give rise to some of the symptoms attending 
gangrene. Ptomains may be formed wherever decomposition is 
taking place. 

The most important feature of gangrene is the line of demarca- 
tion y for upon it depends the separation of the dead part and the 
subsequent repair. This line appears at the border of the gangren- 
ous area as a red, inflammatory zone. Toward the dead part we 
early find the evidences of separation in the form of a line of lique- 
faction. At this line a groove is formed, which gradually deepens 
until the dead part is thrown off. No matter how large the gan- 
grenous portion may be, if the patient lives sufficiently long, it 
will be thrown off, unless, as is the custom in practice, the part is 
removed by surgical means. 

The process which effects the separation is called ulceration. 
Ulceration is an inflammatory process occurring on surfaces and 
accompanied by softening. Ulcers, under all circumstances, have 
one of two tendencies, either to soften and break down or to heal. 

Clinical CauSOS. — I. Inflammatory processes that are very 
active and in which the blood-vessels do not recover themselves. 

2. Micro-organismal infectio7i y e. g. } hospital gangrene. This 
is an infectious and highly contagious disease, the cause of 
which is probably virulent forms of the ordinary pyogenic micro- 
organisms. 



38 NOTES ON PATHOLOGY. 

3. Traumatism, especially when affecting the large venous 
trunks, and giving rise to coagulation of the blood within them. 
A tight ligature around a limb by pressing directly upon the veins, 
may also lead to gangrene. 

4. Diabetes. This probably induces a condition of the system 
favoring the action of micro-organisms. 

5. Neuropathic causes, as e. g. y in certain bedsores. Bedsores 
may be due simply to pressure maintained for a long time, but there 
is a class of such lesions that occur acutely, and are dependent upon 
disease of the ganglion-cells of the anterior horns of the spinal 
cord (the trophic centers). 



CHAPTER III. 



ELEMENTARY PATHOLOGIC PROCESSES 
AFFECTING THE CIRCULATION. 

LOCAL HYPEREMIA— LOCAL ANEMIA. 

The amount of blood in a part is normally subject to frequent 
changes. These changes become pathologic when they have an 
abnormal cause or when they are excessive. 

HYPEREMIA OR LOCAL CONGESTION. 

This is an excess of blood in a part. 

There are two forms : A. Active. B. Passive. 

A. ActiVO Hyperemia.— The part the seat of active hyper- 
emia is swollen and red ; its temperature is elevated ; there may 
be a sensation of heat or even of pain. 

Hyperemia and its attendant phenomena frequently disappear 
after death, first, because the arteries contract and drive the blood 
into the veins, and secondly, because the blood gravitates to the 
dependent portions of the body. The arterial contraction may be 
so pronounced as to render the part pale. 

This disappearance of hyperemia is frequent in the intestinal 
mucous membrane, and we may find pallor in cases in which we 
would expect hyperemia. The presence of blood in the large 
vessels of an organ is no evidence of ante-mortem hyperemia. To 
establish the latter there must be a filling of the capillaries, pro- 
ducing a uniform redness. We may find the signs of active 
hyperemia preserved in the wall of the intestines in cholera ; also 
at times in the gray matter of the brain. 

Active hyperemia may be (a) Idiopathic, (f) Collateral. 

(39) 



40 NOTES ON PATHOLOGY. 

Idiopathic hyperemia is caused by an impairment of the resist- 
ing power of the arteries leading to the affected part. The loss of 
resistance may be caused : 

1. By agencies acting directly on the muscular coat of the 
arteries causing paralysis. These agencies may be 

(a) Mechanical, as a blow, which causes a momentary contrac- 
tion of the arteries, then dilatation and hyperemia. 

(j3) Heat. This, too, produces a primary contraction, then a 
dilatation. 

(y) Drugs, as atropin. 

(5) Diseases of the coats of the arteries, especially chronic 
inflammation with fatty degeneration. 

All these causes may be aided by a general increase in blood- 
pressure. 

2. By disturbances of the nervous system. These are of two 
kinds, those that paralyze the vaso-constrictor nerves — neuro- 
paralytic hyperemia ; and those that stimulate the vaso-dilator 
nerves — neurotonic hyperemia. 

The nervous forms of hyperemia occur frequently in connection 
with nervous diseases ; they are very commonly reflex in origin. 

(b) Collateral hyperemia. This is brought about by obstruction 
in the arterial circulation of a neighboring organ, e.g., obstruction 
of the right renal artery causes an excess of blood to go to the left 
kidney. 

Active hyperemia may lead (i) to hypertophy, (2) to cloudy 
swelling, by over-stimulation of the nutritive functions of the cells, 
and (3) to inflammation. 

B. Passive Hyperemia, Stasis, or Venous Conges- 
tion. — This is caused by obstruction of the venous circulation 
preventing the outflow of blood from an organ or part. 

On account of the free venous anastomosis, passive congestion 
is not readily produced. Besides the local causes there must 
always be some general conditions favoring the congestion. These 
general conditions are 

1 . Valvular heart-disease. 

2. The action of the muscles. 

3. Disturbances of the pulmonary circulation, and 

4. Gravity. 



LOCAL ANEMIA OR ISCHEMIA. 41 

The local causes are (1) Pressure upon the veins. Pressure 
more easily compresses the veins than the arteries, the latter having 
more resisting walls. 

2. Disease of the vessel- walls. 

3. Thrombosis. 

Morbid Anatomy.— The affected part is swollen and 
of a bluish color, and its temperature is lower than normal. The 
bluish color is apt to disappear post-mortem after a section of 
the organ has been made, on account of the oxidation of the hemo- 
globin. Passive congestion may lead to (a) cloudy swelling, (b) to 
atrophy, (c) to degenerations, and (d) to necrosis, e. g., to moist 
gangrene. 

Brown atrophy is a variety of atrophy due to long-continued 
congestion and associated with excessive pigmentation. Prolonged 
congestion leads to the formation of new connective tissue and thus 
gives rise to cyanotic induration of the affected organ. 

Post-mortem hypostasis, or cadaveric lividity. — This is a gravita- 
tion of the blood to the dependent parts of the body after death. 
It must be distinguished from bruise marks, the result of injuries 
during life. The following are the differential characters : 

1. The cadaveric lividity occurs only in the dependent portions 
of the body. 

2. The blood is fluid and can be pushed from one point to 
another, while in the bruise the blood is extravasated and cannot be 
pushed aside. 

3. When the part is cut the blood runs out in case of cadaveric 
lividity, but not in that of a bruise. 

LOCAL ANEMIA OR ISCHEMIA. 

This is due to a diminution in the caliber of the blood-vessels 
leading to the affected part. 

Causes. — I. Pressure on the arteries, as by a tumor or by a 
swelling of the surrounding tissues. 

2. Changes in the walls of the blood-vessels, as {a) chronic inflam- 
mation, (b) tumors. 

3. Obstruction within the blood-vessels, (a) by a thrombus or (b) 
by an embolus. 

4. Nervous disturbances, producing a contraction of the muscu- 
lar coat of the arteries. The causes generally act reflexly through 



42 NOTES ON PATHOLOGY. 

the nervous system, as, e. g. y anemia of the brain from disturbance 
in the intestines. Gastric and uterine diseases frequently cause 
anemia reflexly. Hysteria, especially the grave forms of the 
disease associated with anesthesia (hemianesthesia), gives rise to 
ischemia, which may be coextensive with the loss of sensation. 

Collateral Anemia. This is quite rare and is brought about 
by congestion of a neighboring or related organ. Dilatation of the 
vessels of the abdomen induces anemia of the brain. 

The development and character of the local anemia depend 
upon the facility with which a collateral circulation can be estab- 
lished. If the latter is ample, the anemia is not marked. In organs 
possessing so-called terminal or end-arteries the collateral flow is 
established with difficulty. There is no true collateral circulation 
in these cases, no communication by large branches, but only 
through the medium of capillary vessels. Obstruction of such 
arteries leads to anemia of the part supplied. 

Morbid Anatomy. — The anemic organ is pale, its tempera- 
ture is lowered, and its size diminished. Later, when necrotic 
changes develop, the part may become swollen and larger. In 
cases where the stoppage of the vessel is complete, as by a thrombus 
or an embolus, an infarct is produced, which may be anemic or 
hemorrhagic. 

THROMBOSIS. 

Thrombosis is the coagulation of the blood in the circulatory 
stream. Consisting in the formation of fibrin, it is an example of 
coagulation-necrosis. 

Seats. Chambers of the heart, veins, arteries and capillaries. 

Morbid Physiology. — The process of coagulation within 
the vessels is the same as that occurring in shed blood. In order 
to understand it, it is necessary to consider those conditions which 
prevent coagulation in the physiologic state. It is generally 
accepted that the fluidity of the blood depends upon the mainten- 
ance of a normal, vital relation between the blood and the endo- 
thelial lining of the vessels. Any disturbance of this relation 
leads to thrombosis. 

The disturbance may be : 

(a) In the vessel-walls. 

(b) In the blood. 



THROMBOSIS. 43 

(a) Changes in the vessel-walls. These are principally those 
that bring about a roughness and desquamation of the endothe- 
lium of the intima, as occurs in acute and chronic inflammation of 
the vessels, and in injuries. 

(8) Changes in the blood. These may affect (a) the chemical 
composition, (j3) the rate of flow. 

(a) Changes in chemical composition. Chemical changes pre- 
disposing to thrombosis may be produced (1) by the injection of 
blood-serum from one species of animal into the blood-vessels of 
another species. The serum probably acts upon the leukocytes 
of the injected animal in such a way as to liberate fibrin-ferment. 
The blood of certain species of animals has a greater tendency 
than that of others to produce coagulation. (2) By the injection 
of certain substances that destroy the corpuscles. (3) By extensive 
burns. 

(f) Change in the rate of flow. This is probably the most fre- 
quent cause of the thrombi seen post-mortem, which are formed 
during the closing hours of life, in the agonic period. 

When the blood stream flows with its normal velocity, the red 
corpuscles occupy the center, or the axial current, while the white 
corpuscles and blood-plaques are at the periphery. This difference 
in position is due to physical causes ; the heavier elements, the red 
corpuscles, seek the center of the stream ; the lighter, the white 
corpuscles and plaques, the periphery. When the current is slowed, 
the corpuscles at the periphery of the stream show a tendency to 
fall against the vessel-wall. The plaques are the first to be deposited, 
and by a process of agglutination, a form of hyaline degeneration, 
which occurs when the flow is not of the normal rapidity, adhere 
together. This agglutination constitutes the first step in the produc- 
tion of the thrombus. The resulting mass projects as a coral-like 
formation from the inner wall of the vessel. To this mass leuko- 
cytes readily adhere ; changes take place in the latter by which 
certain substances are liberated : fibrin is formed and deposited on 
the coral-like projection. In this way a white thrombus is formed; 
at times many red corpuscles are caught in the clot, and the latter 
then has a red or marbled color. 

It is easily comprehended that whenever the current is slowed, 
chemical changes will rapidly be induced in the blood, and will con- 
tribute to the formation of the thrombus. As soon as there is any 
departure from the normal composition of the blood, the vessel-walls 



44 



NOTES ON PATHOLOGY. 



cease to be properly nourished, and anatomic changes take place in 
the endothelial lining, which further favor coagulation. Thus 
it is evident that all the causes of thrombosis are intimately cor- 
related, and that, given any single one, the others must of necessity 
follow. 

Morbid Anatomy. — Thrombi are made up of layers of 
different color, and present radiating trabeculae of fibrin that may 
be visible to the naked eye. The color of the clot depends upon 
the presence or absence of red corpuscles, which 
in turn is probably dependent upon the rapidity 
of the current at the time of clotting. The longer 
the clot remains in the living body, the whiter, 
firmer, dryer, and more adherent to the vessel- 
wall it becomes. 

The coagula formed after death in the heart 
and large blood-vessels are soft, jelly-like, not 
adherent, dark-red in color, and are known as 
"currant-jelly" clots. During the agonic period 
clots are deposited which are light in color, from 
the whipping-out of the red cells, are soft, jelly-like, 
Obstructing thrombus edematous, and almost diffluent. These are the 
in the femoral and « cn i c ken-fat " clots ; frequently they are com- 

saphenous veins; also r ± * * 

a thrombus on one of bined with currant-jelly clots. The thrombi formed 
evaves. {Zugier.) during jjf e are d rve r, denser and more adherent, 
and on microscopic examination are found to contain more fibrin 
and more leukocytes. 

Thrombi are classified in various ways : 

1. According to shape: 
(a) Occluding. 

(ft) Parietal — one formed only on one side of the vessel-wall, 
or produced by the washing away of a part of an occluding 
thrombus. 

(c) Valvular. A form of parietal thrombus taking the shape 
of a valve of a vein or a heart-valve. 

id) Channeled or tunneled. A clot may be deposited in an 
annular form or an occluding thrombus may become hollowed out. 

2. According to period of formation : 

(a) Primary. One formed at the original seat of lesion. 

(b) Secondary. That deposited on the primary thrombus and 
extending to the nearest branch. 




EMBOLISM. 45 

3. According to etiology : 

(a) Infecting. 

(b) Non-infecting or mechanical. The infecting thrombus is 
produced by micro-organisms, which act upon the leukocytes and 
cause the liberation of fibrin-ferment. The first results of the 
thrombus are mechanical, but the presence of the bacteria speedily 
leads to inflammatory changes, which frequently terminate in sup- 
puration at the site of the thrombus, and also induce a general 
infection of the system, with or without the formation of multiple 
abscesses. 

Thrombi have a tendency to undergo certain changes : 

(a) Organization, i. e., the growth of new connective tissue 
into the thrombus from the walls of the containing blood-vessel, 
the fibrin of the clot acting as a frame-work for the developing 
tissue. 

(b) Liquefaction. This affects chiefly the interior of the 
thrombus and leads to the formation of a reddish, puriform fluid. 
In heart-clots the process may give rise to large cavities filled with 
fluid. The softening is, in some instances, caused by micro-organ- 
isms ; in others, of obscure nature, micro-organisms are absent. 

Clinical Causes. — 1. Cachectic and marasmic conditions, in 
which we have a slowing of the current and an alteration in the 
character of the blood (marasmic clots). 

2. Chronic diseases of the heart, associated with changes in the 
endocardium or the valves. 

3. Acute endocarditis. 

4. Atheroma. 

5. Injury to the walls of the blood-vessel, as in ligation. 

6. Obstruction or dilatation of the veins. 

7. Micro- organisms. 

EMBOLISM. 

Embolism is the stoppage of a blood-vessel by a fragment of 
fibrin or other material carried in the circulation. The obstructing 
particle is termed an embolus. 

Emboli in the majority of instances follow the course of the 
circulation : in the arteries, toward the periphery, in the veins, toward 
the heart. Exceptionally there is a reverse flow in the large veins 
by which emboli may be carried into the latter from the heart. As a 



46 NOTES ON PATHOLOGY. 

rule emboli consist of fibrin derived from a thrombus, but fragments 
of tissue, of tumors, particles of fat or of pigment, and micro- 
organisms, may be carried in the blood-stream and constitute 
emboli. 

Owing to their anatomic position certain vessels are more 
frequently the seat of embolism than others. Thus the left carotid 
artery is more prone to receive emboli than the right ; the left iliac 
than the right ; the right pulmonary than the left. 

The superior and inferior mesenteric arteries are practically 
exempt from embolism. In the brain emboli follow as a rule the 
channel of the left middle cerebral artery. 

Occasionally a large vessel is obstructed by an embolus, but 
more commonly we meet with many small emboli which give rise 
to miliary embolism, a condition not rarely seen in ulcerative endo- 
carditis. The symptomatology of miliary embolism is very variable 
and obscure. By some it is held that chorea is a possible conse- 
quence of miliary emboli of the brain. 

Emboli are (a) simple, or mechanical or (b) specific. The former 
produce merely obstruction — if in a terminal artery, the result 
will be an anemic or a hemorrhagic infarct* The latter contain 
micro-organisms, which set up, at the point of lodgment of the 
emboli, the same changes as in the original seat whence they were 
derived, most frequently small abscesses {metastatic abscesses). 

HEMORRHAGE. 

This is an out-pouring of blood from the blood-vessels. 
Hemorrhages are divided as follows : 

I. According to source : 

i. Arterial. 

2. Venous. 

3. Capillary. 

II. According to the mode in which the blood leaves the vessels : 

1. Hemorrhage by laceration ox per rhexin. 

2. Hemorrhage by diapedesis — a gradual extrusion of the blood 
through the vessel-walls (capillaries and veins) without previous 
rupture. 



* Anemic infarction has been discussed under coagulation necrosis ; hemorrhagic infarction will be 
described under hemorrhage. 



HEMORRHAGE. 47 

III. Hemorrhage may be 

1. From free surfaces. 

2. Into tissues — interstitial. 
Hemorrhage from free surfaces may be 

(a) External, as epistaxis, hematemesis, hemoptysis, menor- 
rhagia, metrorrhagia, hematuria. 

(b) Internal, as hematometra, hemothorax, hematocele, hemo- 
pericardium. 

2. Interstitial hemorrhage. 

(a) The hemorrhage may form a cavity for itself (hematoma). 

(b) It may infiltrate the tissues (hemorrhagic infiltration or 
extravasation). Various terms are employed to designate hemor- 
rhagic infiltration. 

(a) Ecchymosis is applied to localized hemorrhages beneath 
surfaces. 

(/3) Petechiae — are small punctiform hemorrhages beneath the 
skin. 

(y) Suffusion or sugillation — is an extensive hemorrhage be- 
neath the surface. 

(5) Hemorrhagic infarct — a well-circumscribed, wedge-shaped 
.area of hemorrhage, the result of embolism or thrombosis. 

According to causation hemorrhages are divided into 

1. Traumatic — due to direct injury received from without. 

2. Essential, idiopathic, or autoge?ious — those the causes of 
which reside within the body. 

The causes of essential hemorrhage are : 

(a) Excess of blood-pressure, (a) as in whooping-cough (hemor- 
rhage into conjunctiva, hemoptysis); (/3) in mitral stenosis (hemo- 
ptysis, epistaxis, hematemesis) ; (y) in cirrhosis of the liver (from 
esophageal veins, from stomach, from intestines). 

(b) Diseases of the vessel-walls, (a) Atheroma ; (j8) inflamma- 
tion ; (y) infectious diseases. The last cause alterations in the 
vessel-wall and, probably, also in the blood itself. Examples : 
hemorrhagic or black small-pox ; yellow fever. 

(c) Changes in the blood — as in the so-called hemorrhagic 
diseases, hemophilia, purpura, and scurvy. Tne nature of the 
changes leading to the bleeding in these cases is not clearly under- 
stood. Very probably there is also a disturbance in the walls of 
the blood-vessels. Purpura and scurvy, particularly the latter, may 
be due to micro-organismal infection. 



48 NOTES ON PATHOLOGY. 

(d) Neurotic disturbances , as (a) in hysteria, in which hemor- 
rhage may occur in strange localities — sometimes from the hands 
and feet, simulating the crucifixion ; (j8) in acute insults to the 
nerve-centers of the brain, as in apoplexy, which at times leads to 
hemorrhage from the lungs and stomach. 

(e) Embolism or thrombosis of an artery — causing hemorrhagic 
infarction. 

Terminations of Hemorrhage, If death does not result/ the 
bleeding is stopped by thrombosis. The clot then acts as a foreign 
body and is gradually removed by organization. It is not itself 
converted into fibrous tissue, but merely serves as the skeleton or 
framework for the newly forming connective tissue. The vessel is 
eventually changed into an impervious fibrous cord. 

Fate of the effused blood. In interstitial hemorrhage the blood 
is usually removed by absorption, but the blood pigment, in the 
form of crystals or granules, remains for a long time. Connective 
tissue replaces any portions of the organ or part that were destroyed 
by the hemorrhage. 

In the case of a hematoma the blood may remain in the cavity 
for a long period. At times it becomes surrounded by a connective 
tissue capsule, the blood-pigment is absorbed, and a clear cyst is 
produced. The fluid of the cyst or the original hematoma may be 
absorbed, and the gap filled up by the process of organization. 

The effusion of the blood in the serous cavities produces 
scarcely any inflammatory reaction ; the blood is as a rule rapidly 
absorbed. Hence it is unnecessary to tap a serous sac for the 
evacuation of blood. 



HEMORRHAGIC INFARCTION. 

A hemorrhagic infarct is a wedge-shaped infiltration of blood, 
brought about by the obstruction of the artery leading to the 
affected area. The cause of the obstruction is usually an embolus 
or a thrombus. A rapid degeneration takes place in the walls of 
the blood-vessels of the region supplied by the occluded artery, and 
renders possible the occurrence of hemorrhage from these vessels. 

To explain the extravasation into an area from which the 
natural blood supply is cut off, the following theories have been 
advanced : 



HEMORRHAGIC INFARCT. 49 

i . The stoppage of the current in the artery produces a condi- 
tion of negative pressure, by reason of which blood flows back from 
the veins. 

2. The blood flows into the area from the neighboring capil- 
laries. 

3. The sudden lodgement of an embolus provokes a reflex con- 
traction of all the arteries and veins beyond the seat of obstruction 
and even above it, i. e. f to the proximal side of it, whereby an excess 
of blood is forced into the capillaries, and they rupture. 

The majority of infarcts are best explained by the last theory. 

Morbid Anatomy. — (a) Macroscopy. The infarct is pyra- 
midal in shape, the base of the pyramid being directed to the peri- 
phery of the organ ; it is raised above the surrounding surface, and 
is firmer and darker in color. 

(b) Microscopy. We see the breaking down of the red blood- 
corpuscles ; pigment is present, and fibrin. 

Terminations. The infarcted area is converted into a cyst or is 
removed and replaced by a scar. 

The hemorrhagic infarct is produced by mechanical obstruc- 
tion. If an infecting embolus lodges in a vessel it usually sets up 
inflammatory changes. At times we find some extravasation of 
blood, especially at the periphery ; while at the center, at a point 
corresponding to the seat of the infecting embolus, the changes 
peculiar to the infectious agent are developed — generally an 
abscess. 

Hemorrhagic infarcts are most common in the lung, kidney, 
spleen, and brain. 



CHAPTER IV. 



COMPOSITE MORBID PROCESSES. 

In the preceding part of the subject, the cell was looked upon 
as an entity, and was not considered in its relation to other cells. 
In composite morbid processes we deal with the pathology of the 
tissues rather than with that of the cells. Hemorrhage and gan- 
grene are, in reality, not simple morbid processes, but they are most 
conveniently studied with that group. 

The composite morbid processes are three in number — inflam- 
mation, regeneration, and tumor formation. In all of them we have 
hyperplasia of tissues. 

Inflammation is an eliminative process ; regeneration, since it 
produces new tissue, is formative ; tumor-formation, leading to the 
development of useless tissue, is termed pseudo-formative. 

INFLAMMATION. 

Inflammation is the reaction of the parablastic tissues to the 
action of irritants, when this reaction is attended by an overfilling 
of the blood-vessels with blood, a change in their walls, an extru- 
sion from them of a modified plasma and of leukocytes, and a 
proliferation of the connective tissue-cells. These changes have for 
their object the removal or isolation of the source of irritation. 

The changes in the archiblastic tissue are secondary, as far as 
the actual changes in inflammation are concerned. Frequently the 
parenchyma is primarily affected, but it should then be looked upon 
as the cause of the inflammation, constituting the source of irrita- 
tion which excites the inflammatory changes in the parablast. 

Sources of Irritation. 

id) Those arising within the body, viz. : Portions of tissue or 
abnormal metabolic products that have become unfit for the normal 
functional activity, and require removal. 

(f) Micro-organisms. 

(So) 



INFLAMMATION. 51 

Although these two groups are quite distinct in character, they 
are separated with difficulty as causes of inflammation ; we find 
them nearly always associated together. The reasons for this are 
plain : tissues unfit for further use act as irritants and inaugurate 
the inflammatory process, but at the same time they offer a favorable 
soil for micro-organisms ; both then seem to act together. On the 
other hand, if micro-organisms enter the tissues, one of their first 
effects is to cause the death of cells, and then both sources of irri- 
tation are again combined. 

Micro-organisms, whatever their exact relation, play a very 
important part in the inflammatory process. Inflammation as it 
was described by the ancients, with its four cardinal symptoms, 
referred to the abscess, which is always micro-organismal in origin. 

The sources of irritation arising within the body are due to two 
causes which may be termed (a) external and (b) internal. 

(a) External — traumatism. This primarily causes a destruc- 
tion of cells ; the latter then set up the inflammation. 

(b) Internal. 1. Disttirbances of circulation — as the stoppage 
of a vessel by an embolus, leading to hemorrhagic or anemic 
infarction. 

2. Disturbances of innervation, i. e. y interference with the trophic 
function of the nerves. This we see in the bed-sores of myelitis — 
the dead tissues, for their removal, require the inflammatory 
process. 

3. Disturbances of metabolism. These are not clearly under- 
stood. In certain diseases abnormal products are elaborated which 
act on the tissues and start up the inflammatory process. 

In Bright's disease we may have inflammation of the serous 
membranes ; gout leads to chronic inflammatory changes in the 
kidney — the gouty kidney ; cirrhosis of the liver is sometimes 
associated with obscure inflammations in other organs. 

Morbid Anatomy. — («) Microscopy. The changes in inflam- 
mation are generally described under three separate heads : 

1. Vascular changes. 

2. Changes in the parablastic tissues. 

3. Changes in the archiblastic tissues. 

1. Vascular Changes. The first change that is apparent is 
a contraction of the blood-vessels. This is merely accidental, being 
due to a reflex action excited by the irritant ; it is no part of the 



$2 NOTES ON PATHOLOGY. 

inflammatory process, and may disappear without being followed 
by inflammation. The next change is a dilatation of the blood- 
vessels, with an increased activity of the circulation at the periphery. 
This dilatation is both active, or idiopathic, and collateral — idiopathic, 
because of the increased activity of the circulation in that region ; 
collateral, because there is in the center a tendency to stasis. In 
the central area the dilatation is passive, and is due to a simple 
yielding of the vessels. Eventually there is complete stasis in the 
center. The filling of the blood-vessels causes them to become 
wider, and some that were invisible before appear now as fine red 
lines. 

The slowing of the current produces the same phenomenon as 
in thrombosis, namely, a tendency of the white corpuscles to fall 
against the vessel-wall. This tendency is termed the peripheral 
drift of the leukocytes. As soon as the circulation is completely 
arrested, the leukocytes begin their ameboid movements, and 
wander out through the wall, and also into the center of the vessels. 
Normally, the blood-vessel walls constitute a barrier to the passing 

out of cells, but when the blood 
supply is arrested they become 
more yielding, and the leukocytes 
pass out through the softened 
cement-substance between the 
endothelial cells. This wander- 
ing-out occurs especially from the 
smaller veins and capillaries and 
gives rise to a dense accumulation 
of cells about these vessels. As 
early as ten hours after the appli- 
cation of the irritant we may find 
the capillaries embedded in compact cylinders of round cells. 

There is also an exudation through the vessels of a modified 
plasma, which is richer in albumin and higher in specific gravity 
than the plasma of dropsy. This fluid may remain in the liquid 
state, when we speak of inflammatory edema, or it may coagulate 
and form " lymph." Whether the one or the other occurs depends 
on the character of the inflamed tissues and on the cause of the 
inflammation. In diphtheria we have coagulation. 

There is also, in some inflammations, particularly those of an 
intense degree, a diapedesis of red corpuscles. 




INFLAMMATION. 53 

Historical. — The outwandering of the leukocytes was first observed by Waller, in 
1823; subsequently by Dutrochet and by Addison. None of them, however, recognized 
the importance of the phenomenon, and it was left for Cohnheim to point out, in 1867,. its 
true significance. He may, therefore, be justly considered the actual discoverer. 

Another important and essential part of the vascular changes 
consists in a softening of the walls of the blood-vessels, especially of 
the cement-substance holding the endothelial ceils together. 

(b) Naked-eye phenomena and symptoms. These are redness, 
swelling, pain, and heat, and may nearly all be accounted for by 
the histologic changes described. 

(1) Redness. This is due to the overfilling of the blood-vessels. 
The outer area is lighter, the central darker in color. 

(2) Swelling. This is the result of () the excess of blood in 
the vessels, (3) the passing out of plasma and corpuscles, and (y) the 
multiplication of cells. 

(3) Pain. This is due to pressure exerted by the swollen 
tissues upon the terminal nerves, or by an action of irritant products 
upon the nerve-endings. 

(4) Heat. It is difficult to determine whether this is due to 
increased heat-production or increased heat-elimination. In the 
central area of stasis there can be no augmented production, but 
at the periphery the active chemical changes may lead to an 
increased production of heat. 

Morbid Physiology. — The phenomena which characterize 
inflammation can only occur when the blood-current is slowed. But 
this alone is not sufficient, for a similar condition of slowing obtains 
in some hyperemias, yet in them the blood is retained within the 
vessels. There must be some alteration in the vessel-wall to allow 
the emigration of leukocytes and the exudation of plasma. Between 
the blood and the tissues there exists normally a reciprocal, meta- 
bolic current, over which the endothelial cells of the blood-vessels 
have considerable control, i. e. y the lymph bathing the tissues does 
not pass out through the capillary walls by mere filtration, but 
owing to a selective action of the endothelial cells. The entrance 
of waste products into the blood stream is likewise not a simple 
physical process. The function of the endothelial cells is to a 
certain extent comparable to that of the cells of secreting glands. 
Any disturbance in the metabolic current between blood-vessels 
and tissues brings about changes that may pass on to inflammation. 



54 



NOTES ON PATHOLOGY. 



The disturbance may give rise to the passing out from the vessel of 
substances that should be retained ; or substances are retained that 
should be extruded ; or, as seems most probable, something is 
formed in the tissues which, in its passage into the vessel, causes 
serious changes in the vessel-wall. As the normal circulation de- 
pends upon the physical and chemical relations between the blood 
and the vessel-wall, such a change rapidly leads to a slowing and, 
finally, to a stagnation of the blood-current. This induces further 
alterations in the endothelial cells, which may undergo various ele- 
mentary morbid changes. 

While the wandering-out of the leukocytes is in part accounted 
for by their power of ameboid movement, there is another factor : 
the presence of certain substances termed chemotactic ', which stimu- 
late the emigration of these cells. 

Chemotaxis is the property possessed by certain bodies of at- 
tracting or of repelling the leukocytes. It is, therefore, of two 
kinds : (a) Positive chemotaxis — that which attracts the leukocytes ; 
(b) Negative chemotaxis — that which repels them. 

The experiments to determine the chemotactic nature of different 
substances are performed somewhat as follows : Small capillary 
glass tubes are filled with the material to be tested and introduced, 
with all antiseptic precautions, into the loose cellular tissue, or into 
the anterior chamber of the eye. They are allowed to heal in and 
are subsequently broken. If the substance used is positively 
chemotactic, the ends of the glass tube will become packed with 
leukocytes, while if the material is negatively chemotactic, the tube 
will remain empty. 

The positive chemotactic substances as a rule are component 
parts of cells ; the products of cell-activity, or waste-products of 
metabolism, as urea, are negatively chemotactic. The positive 
chemotactic substance is a nitrogenous compound (certain non- 
nitrogenous substance used experimentally manifest positive 
chemotaxis) ; it may be nuclein arising from cell-nuclei, or a com- 
plex proteid substance derived from the cell-protoplasm. The 
most active chemotactic substances resemble vegetable casein. In 
inflammation these bodies are set free and exert a positive chemo- 
tactic action. 

Among positive chemotactic substances may be named gluten 
casein, legumin, bone gelatin, isinglass, alkali albuminates from 
muscles, liver, and lung, and hemi-albumoses. Since bacteria are 



INFLAMMATION. 55 

vegetable cells with large nuclei, they contain a very positive 
chemotactic substance. 

Negatively chemotactic are ammonia and some of its salts, as 
the butyrate and valerianate, trimethylamin, urea, ammonium urate, 
peptones, tyrosin, etc. 

While nearly all bacteria possess positive chemotactic proper- 
ties, some present this quality in a much more marked degree than 
others. Thus the group of pyogenic bacteria and the bacillus of 
tuberculosis are strongly chemotactic. 

The positive chemotactic substance may be extracted from 
bacteria. It has been obtained from the bacillus pyocyaneus by 
treating the culture with a dilute alkaline solution, precipitating it 
from the latter with weak acids, and again dissolving it in alkalies. 

In order that chemotaxis may become operative and cause an 
outwandering of leukocytes, the other changes described must be 
present, viz., a slowing of the blood-current and an alteration in the 
vessel-wall. 

Changes in the Fixed Connective Tissues.— These are 

of two kinds, (a) degenerative and (b) proliferative. 

The degenerative changes are the different forms of degeneration 
and necrosis already described under the simple pathologic pro- 
cesses, chiefly coagulation necrosis, liquefaction necrosis, and fatty 
degeneration. 

The regenerative changes consist in a multiplication of the 
fixed connective tissue cells, and have for their object the repair of 
the parts destroyed. They are a part of inflammation only within 
certain limits ; beyond these they belong to regeneration. 

The proliferation of the connective tissue cells is a marked fea- 
ture of inflammation, and manifests itself very early in the process 
by karyokinetic changes. The nucleus of the connective tissue 
cells is large, vesicular, and stains feebly, the periphery staining best. 

The leukocytes have generally multiple nuclei, or the nucleus 
may be single, but indented and irregular. They stain intensely. 
The greater the number of new connective tissue cells, the 
more likely is regeneration to take place ; if the multinuclear cells 
are in excess, suppuration will probably be the termination. 

The accumulation of cells in an inflammatory area is so great 
and takes place with such rapidity, being quite marked in ten 
hours, that the explanation of their origin from only two sources, 



56 NOTES ON PATHOLOGY. 

the emigration of leukocytes and the proliferation of fixed connec- 
tive tissue cells, seems scarcely sufficient. The number of leuko- 
cytes must obviously be limited on account of the stasis in the 
blood-vessels, and the number of connective tissue cells can also 
not be very great on account of the comparatively few cells from 
which they spring. 

These two processes thus seeming inadequate, the theory has 
been advanced, and on very good grounds, that we have in the con- 
nective tissue certain " slumbering-cells " (Schlummerzellen), germinal 
particles of cells, which cannot be demonstrated with the ordinary 
nuclear stains, but which under the influence of the irritation 
present in the inflammatory process, develop into cells. We recog- 
nize in bacteria a condition quite analogous to this : the germinal 
particles or spores of bacteria do not stain under ordinary circum- 
stances, and generally escape detection ; but under favorable con- 
ditions they are capable of developing into perfect bacteria. 

Some of the cells in the inflamed area, principally the leuko- 
cytes, have a tendency to degenerate — they undergo fatty degener- 
ation, or take part in the coagulation necrosis or liquefaction 
necrosis. It is possible that they may contribute to the nutrition 
of the fixed connective tissue cells, which are associated with 
regeneration. 

Changes in the Intercellular Substance. This may undergo any 
of the degenerations, but as a rule it presents the following three 
changes : 

1. Liquefaction necrosis. In this it melts away and contributes to 
the formation of pus. 

2. Coagulation necrosis. It may suffer coagulation necrosis 
alone, or with the cells of the connective tissue, or with the fluid 
plasma. 

These two are the destructive changes ; the cells may, ot 
course, participate in them. 

3. // may undergo a reparative change, and contribute the basis 
of the regenerative process, forming the network in which the cells 
find support. 

Inflammation lays the foundation for the regenerative process 
in a double manner : (1) by furnishing certain cells ; (2) by supplying 
a skeleton-ivork for these cells, which holds them together. 

Is the cellular accumulation absolutely characteristic of 
inflammation ? No, for we find normally such collections of round 



SUPPURATION. 57 

cells, " lymphoid tissue," especially in the mucous membrane of 
the digestive tract. They are either distinct lymphoid follicles, 
limited by a wall, or have no special structure and are without wall. 
The latter are with great difficulty distinguished from the inflamma- 
tory accumulation. The diagnosis is based on the fact that the 
lymphoid whirls are isolated and surrounded by normal tissue, 
while the inflammatory areas are irregular, and fade gradually into 
the surrounding tissue. It is, however, possible that the lymphoid 
whirls are the result of an attempt to eliminate an irritant, perhaps 
bacteria. 

Inflammation in tissues devoid of blood-vessels, as the cornea 
and cartilage, presents all the phenomena that have been described. 
The chemotactic influence acts, in the case of the cornea, on the 
leukocytes in the blood-vessels at the periphery, and causes them to 
wander in along the lymphatic channels. The proliferation of the 
fixed connective tissue cells is also observable. 

Naked Eye Appearances of Inflammation.— Inflam- 
matory exudate, or inflammatory infiltration, is the name given to 
all the materials thrown out in inflammation — both the cells and the 
fluid. Different names are employed to designate the nature of the 
fluid element — serous, sero-fibrinous, fibrinous or croupous, and 
hemorrhagic. Inflammatory edema indicates the presence of a 
large amount of fluid infiltrating the tissues. 

Various names are given to the cellular element: cellular 
infiltration, cellular exudate, round cell infiltration, small cell infil- 
tration, granulation tissue. 

SUPPURATION. 

Suppuration is a liquefaction necrosis of the inflammatory exu- 
date. It may occur in the following localities : 
i. On free surfaces — 

(a) On serous membranes, when it takes the name of the 

membrane afTected, e. g., pyothorax, pyopericardium. 

(b) On mucous surfaces, when it is termed purulent catarrh. 

(c) On free surfaces, with loss of tissue — ulceration. 
2. Within tissues — 

(a) As a circumscribed collection of pus — abscess. 

(b) As a diffuse infiltration — purulent edema, purulent in- 

filtration, or phlegmon. 



58 NOTES ON PATHOLOGY. 

Suppuration may spread from the original seat to neighboring 
tissues along the lymphatic channels, this being most apt to occur 
when the primary process is not sharply circumscribed. When the 
process is circumscribed, we find the pus separated from the healthy 
tissues by a line of demarcation, termed pyogenic membrane. 

In this pyogenic membrane one of two processes is going on 
— either a liquefaction necrosis, when the suppuration is spreading, 
and the line is truly pyogenic, or regeneration, when we find the 
uninuclear cells originating from the connective tissue in excess, 
and the line is healing or granulating. 

These two processes are well represented in ulcers and in 
abscesses. From a pathologic standpoint, ulcers are divisible into 
(a) those that are spreading, in which the pyogenic membrane is 
liquefying, and (J?) those that are healing, in which the line is 
forming granulations. Some of the clinical varieties of ulcers are 
the serpiginous, diphtheritic, gangrenous, fungous, indolent, and 
varicose. 

The wall of an abscess is analogous to the floor of an ulcer — 
if the abscess is spreading, the membrane is pyogenic ; when the 
abscess is healing, it is regenerating. Frequently both processes 
are going on at the same time, which is in accord with the clinical 
history of abscess. An acute abscess does not stand still, but 
spreads until it reaches the surface and discharges. This tendency 
of an abscess to reach the surface, technically termed pointing, de- 
pends upon changes in the circulation. An abscess is in the way of 
its own circulation. The blood comes from below, hence the deeper 
layers are better supplied with nutrition and are able to organize. In 
the upper layers the abscess presses upon the smaller blood- 
vessels, and the tissues break down from want of food supply. 

Looking at pointing from this standpoint, we can understand 
the peculiar direction which abscesses sometimes take. Abscesses 
near the intestines or the bronchi, especially if acute, do not tend 
to rupture into these tubes, but through the surface, because the 
intestine and the bronchi have their own blood-supply. At times 
the circulation is interfered with, and the abscess breaks into the 
intestine or the bronchus. After the abscess is opened, the pyogenic 
membrane becomes a healing or granulating membrane. The 
broken-down material is comparable to the sphacelus in gangrene. 

Abscesses are divided into (a) primary, those produced at the 
site of the original infection ; and (d) secondary, or metastatic, those 



SUPPURATION. 59 

brought about by the carrying of the infecting agent from the 
primary seat to distant parts. The latter are generally multiple, 
occurring in the lung, kidney, liver, spleen, and elsewhere, and result 
from the lodgement of specific emboli in these organs. 

Clinically, abscesses are divided into {a) hot and (b) cold, (a) 
A hot or acute abscess is one in which active inflammatory processes 
are going on, with liquefaction and the formation of true pus. (b) 
Cold abscesses are such as present no marked evidences of inflamma- 
tion, are not as a rule the result of suppuration, and do not, except 
in rare instances, contain true pus. They are most frequently the 
product of cheesy necrosis brought about by the tubercle bacillus. 
Under certain conditions, however, the tubercle bacillus is capable 
of producing suppuration. 

Etiology Of Suppuration.— Clinically, suppuration is al- 
ways the result of micro-organismal infection. Experimentally, it 
may be produced by proteids extracted from bacteria, by calomel, 
turpentine, sabine oil, etc. 

The micro-organisms which most frequently cause suppuration 
are : 

i. Staphylococcus pyogenes aureus, staph, pyog. citreus, staph, 
pyog. albus. These are widely disseminated, occurring in the air, 
sometimes in water, on the surface of the body, and in cavities 
communicating with the exterior. The distinguishing names are 
given by reason of the color of the cultures on artificial media. 
Staphylococci generally produce circumscribed suppuration, i. e. t 
abscess. 

2. Streptococcus pyogenes. This is found in the same places as 
the staphylococcus, but in less abundance. It occurs in long and 
in short chains, the former being more virulent. The suppuration 
produced by it is diffuse — a phlegmon. It is probable that the 
streptococcus of erysipelas is identical with the streptococcus 
pyogenes, for it has been shown that when the former is rubbed 
into the tissues of a rabbit's ear, it causes erysipelas, but when 
introduced elsewhere, it produces diffuse suppuration. The differ- 
ence depends- largely upon the animal, to a much less extent upon 
the micro-organism. 

The staphylococcus and the streptococcus are the most common 
causes of suppuration, and are the bacteria that are commonly 
referred to as pyogenic micro-organisms. Both are readily destroyed 



60 NOTES ON PATHOLOGY. 

by heat, carbolic acid, and other germicides, yet when undisturbed,, 
they retain their virulence for a very long time, from six months to 
a year or more. 

3. Bacillus pyocyaneus. This produces a localized suppu ration , 
in which the pus is of a blue color. In culture media the bacillus 
gives rise to a bluish-green fluorescence. 

4. Pneumococcus. This is normally found in the mouth ; at 
times it produces a localized suppuration, especially in the middle ear 
and in the meninges. 

5. Diplococcus of Friedlander. This occurs in the same localities 
as the pneumococcus, and resembles it closely in its pyogenic 
properties. 

6. Bacillus coli communis. This is a constant inhabitant of the 
intestines. It has been found at times as the cause of purulent peri- 
tonitis, secondary to appendicitis and to intestinal obstruction, and 
is frequently associated with suppuration in the bile-passages. The 
suppuration produced by it is as a rule diffuse and malignant. 

Besides the organisms named there are other bacteria that at 
times cause suppuration, e. g., the bacillus tuberculosis, the bacillus 
of typhoid fever, the gonococcus, and others. 

General results of suppuration : 

(a) Pyemia (literally, " pus in the blood "). This is a condition 
in which the micro-organisms are carried from the original seat and 
set up abscesses wherever they lodge. As a rule there is no pus in 
the blood, but a few cells may occasionally enter the circulation. 

(b) Septicemia. This is a condition produced by the absorption 
of the poisons, or toxins, generated by the bacteria or produced by the 
breaking down of tissues. Neither micro-organisms nor cells are 
carried in the blood. The toxins act chiefly upon the nervous centers. 

In addition to this form of septicemia, which is best termed 
bacterial septicemia, there is another form of poisoning, one not con- 
nected with suppuration, which is known as septic intoxication (auto- 
intoxication). It is not bacterial in origin, but is due to the develop- 
ment within the body, of poisons from faulty metabolism, especially 
from perverted digestion. 

Phagocytosis. — It has been asserted, most earnestly by Metch- 
nikoff, that the leukocytes in inflammation act as phagocytes, i. e., 
that they swallow and digest other cells. At first this theory seemed 
to have a very general application, but further researches have 



CHANGES IN THE ARCHIBLASTIC TISSUES. 61 

lessened its importance. Leukocytes do unquestionably at times act 
as phagocytes in inflamed areas : if the micro-organisms are few 
in number, and their chemotactic and liquefying influence is slight, 
they may be swallowed by the leukocytes. When the bacteria are 
abundant and strongly chemotactic, the leukocytes suffer by the 
contact with them and die. The theory which has replaced that of 
phagocytosis is, that the destruction of bacteria is brought about by 
the juices of the body. It has been found that when micro-organ- 
isms are exposed to the action of the blood-serum, in the absence 
of all phagocytes, they perish just as completely and rapidly as 
when these cells are present. 

It has also been observed that, besides destroying the bacteria, 
the body-juices (the serum) counteract, by means of antitoxins, the 
poisons elaborated by the micro-organisms. The antitoxins chemi- 
cally antidote the toxins. Thus there are two influences involved in 
the recovery from and in the immunity to infectious diseases : (a) the 
bactericidal and (b) the antitoxic. Antitoxins have been found in 
diphtheria, tetanus, pneumonia, typhoid fever, and cholera. The 
substances which destroy the bacteria and neutralize their poisons 
probably arise from obscure metabolic changes in certain cells of 
the body, the resulting products being held in solution in the blood 
and lymph. 

Changes in the Archiblastic Tissues.— The archiblastic 
tissues may be primarily or secondarily affected. The changes are 
usually of a degenerative character, and are not characteristic, but 
are such as can occur under other circumstances, not associated 
with inflammation. The changes may, however, be proliferative ; 
in that case we may properly speak of a true inflammation of the 
archiblast. We find this proliferation in catarrhal inflammation of 
mucous membranes, in catarrhal pneumonia, and in catarrhal 
nephritis. In these the epithelial cells multiply rapidly by karyo- 
kinesis ; many are thrown off and contribute to the formation of 
the inflammatory exudate. In the kidney and lung the exudate 
may be retained in the natural spaces, constituting casts in the 
former, and causing consolidation in the latter organ. The inflam- 
mation is not confined to the archiblast, but the blood-vessels of 
the parablast beneath show all the phenomena of inflammation ; 
there is an outwandering of cells and an exudation of plasma, 
which pass to the surface and contribute to the discharge. 



62 NOTES ON PATHOLOGY. 

Varieties of catarrhal inflammation. i. Mucous catarrh. In 
this we have chiefly a stimulation of the normal function of the 
cells — there is an excessive secretion of mucus ; leukocytes are few. 

2. Purulent catarrh. This is characterized by the great abund- 
ance of leukocytes wandered out from the blood-vessels. Muco- 
purulent cataarh is intermediate between the mucous and the 
purulent forms — it is the variety present in bronchitis. 

3. Desquamative catarrh. This occurs especially in the air- 
vesicles and small bronchioles of the lung and in the tubules of the 
kidney. There is little fluid, but a marked proliferation and des- 
quamation of the epithelial cells which are held in the spaces in 
which they are deposited. 

Depending upon the extent of surface affected, we speak of 
(a) diffuse catarrh, which spreads over an extensive area, and (b) cir- 
cumscribed or follicular y which is confined to small follicles or glands 
in the mucous membrane. The latter is generally desquamative. 

CHRONIC INFLAMMATION. 

This is brought about through {a) the continuous or (o) the 
frequently repeated action of the irritant. In chronic inflamma- 
tion elimination is slow, and time is given for the building up of 
connective tissue, in other words, regeneration plays an important 
part. Some forms of chronic inflammation are readily accounted 
for, as, e. g. } that of the skin produced by the dribbling of urine, 
or the various forms of pneumokoniosis. Micro-organisms, as the 
tubercle bacillus, for instance, may be the cause of chronic inflam- 
mation. There is, however, in the action of these causes, some- 
thing peculiar or specific, some phenomena which are not char- 
acteristic of inflammation, nevertheless they set up a chronic 
inflammation. The tubercle bacillus kills cells, and as these are 
removed with difficulty, time is given for the gradual production of 
connective tissue. 

There is yet another form of chronic inflammation, one in 
which there is a tendency to the permanent overgrowth of connective 
tissue, beginning in the blood-vessels — arte rio- capillary fibrosis — and 
extending to the connective tissue, of nearly all the organs ot 
the body. The blood-vessels are thickened, and the organs hard- 
ened from the excessive formation of connective tissue. This 
tissue contracts and produces cirrhosis of the different organs, 
especially of the liver, kidney, and spleen. 



REGENERATION. 63 

The cause of this generalized form of chronic inflammation is 
not well understood, but it is thought to be the circulation of some 
irritant in the blood, as alcohol, arsenic or, experimentally at least, 
salts of chromic acid. In some cases in which the. irritant is not 
demonstrable, it is surmised that it is generated in the body as the 
result of faulty metabolism, or that certain excrementitious products 
which are not eliminated constitute the irrritant. 

Sources of the Connective Tissue. — i. Multiplication oi 
the previously existing connective tissue — this is the most important 
source. 

2. Obliteration of the blood-vessels and their conversion into 
fibrous cords. 

3. Degeneration of the parenchyma, giving rise to a relative 
increase of the connective tissue. 

4. Organization of the leukocytes — this is problematic. 

Another important feature of chronic inflammation is the hyper- 
plasia of the parenchyma, which goes on hand in hand with the 
degenerative changes, but is much less prominent. 

We find karyokinetic processes in some of the cells. In 
cirrhosis of the liver, for example, the liver cells undergo atrophy 
and are removed, but the cells of the bile-ducts multiply, and new 
ducts are formed. A similar condition is met with in the kidney,, 
in which the cells of the uriniferous tubules proliferate and give 
rise to certain forms of cysts. 

REGENERATION. 

The process of regeneration is best studied in the healing ulcer. 
As soon as an ulcer begins to heal, the cells, which are the basis ot 
regeneration, are held together by a coagulable material, called 
lymph, and are enabled to form their intercellular substance, which 
eventually takes the place of the coagulable skeleton-work. 

Changes in the Cells. The cells gradually assume the perma- 
nent form of the connective tissue, which they replace — fibrous 
tissue, bone, fat, cartilage, or mucoid tissue. Generally a form of 
fibrous tissue is elaborated ; the cells first become oval, then 
elongated, and fibrillae grow out from their ends. They also form 
an intercellular substance, which becomes fibrillated. In this 
manner the granulation tissue, at first cellular, is converted into a 



64 NOTES ON PATHOLOGY. 

tissue in which the intercellular substance forms an important part. 
This new fibrous tissue has a tendency to contract and form cicatri- 
cial or scar-tissue. 

Formation of Blood-vessels. This is the most important ele- 
ment in regeneration. The formation always occurs from pre- 
existing blood-vessels. Quite early in the inflammatory process, as 
soon as the tendency to regeneration manifests itself, the endothe- 
lial cells of capillaries present karyokinetic changes. One of the 
new cells grows into the interior of the vessel, the other protrudes 
outward ; the latter multiplies, and the resulting cells repeat the 
process until a chain is formed, which unites with a similar chain 
from the same or a neighboring capillary. The cells then become 
hollowed out, and a channel is opened — the capillary is then com- 
plete. The loops of capillaries project into the newly formed tissue 
and nourish it, and enable it to form connective tissue. A loop with 
its surrounding cells is known as a granulation. 

The healing of wounds, the organization of a thrombus, and 
the growing together of two serous surfaces, are all comparable to 
the healing of an ulcer. In connection with wounds, we speak (a) of 
healing by granulation, and (b) of healing by first intention. In the 
former there is always some pus, but the tendency to liquefaction is 
overcome and connective tissue formation takes place. If wounds 
are thoroughly cleansed and the edges carefully brought together, 
healing quickly takes place, by the same histologic processes as in 
the healing by granulation. There is a multiplication of connective 
tissue cells and a throwing out of a cement substance holding them 
together. But as the gap to be filled is small, very little granula- 
tion tissue is produced ; indeed, the approximation may be so com- 
plete that none is visible microscopically. Nevertheless, it must 
exist, for a few cells must have been divided by the wound, and can 
only be replaced by karyokinetic changes. Small gaps may be 
filled by the same tissues as those destroyed ; large losses of sub- 
stance heal by cicatrization. 

The study of regeneration is facilitated by the study of the 
formation of connective tissue in foreign bodies. A piece of sterile 
lung, sponge, or elder-pith is introduced into the tissues, preferably 
the peritoneal cavity, of several animals ; the wound is closed, and 
the bodies are removed on different days. The presence of the 
foreign body sets up an inflammatory reaction ; the blood-vessels 
become dilated, and leukocytes and plasma pass out and enter the 



REGENERATION. 65 

foreign body. In twenty-four hours after its introduction we find 
the spaces in the body filled with leukocytes and with a fluid which 
tends to coagulate into fibrin just as far as the leukocytes extend 
in the body. On the second day evidences of regeneration appear 
in a multiplication of the connective tissue cells of the peri- 
toneum. The new cells penetrate into the meshes of the body, 
especially at its periphery, the leukocytes and fibrin occupying the 
center. The connective tissue cells have a tendency to arrange 
themselves along the walls of the spaces in the foreign body. The 
leukocytes degenerate and disappear, perhaps supplying nutriment 
to the connective tissue cells. The fibrin acts as a skeleton work, 
but in time also disappears. Blood-vessels are formed from capilla- 
ries in the peritoneum ; the new cells become elongated, and are 
converted into fibrous tissue. 

The foreign body itself is as a rule gradually removed by solu- 
tion, the rapidity of the process varying with the nature of the 
body. Absorption is more rapid in case of lung than when sponge 
or pith is used. 

If the foreign body is resistant giant-cells appear. These are 
the result of a multiplication of the nuclei of the connective tissue 
cells without corresponding division of the cell-protoplasm. It 
seems that the irritant is capable of causing the nuclei to multiply, 
but either the resistance of the body or the chemical conditions 
present prevent the individualization of the cells. 

Ordinarily, in regeneration, the embryonal tissue is converted 
into fibrous tissue, but any of the connective tissues, bone, carti- 
lage, fat, etc., may be formed from it. 

The cells have received names corresponding to the tissue 
which they are engaged in forming, e.g., fibroblasts, osteoblasts, and 
chondroblasts. 

It is possible for one kind of connective tissue to be formed 
from another, as bone from cartilage, without the intervention of 
embryonal connective tissue, a process that has been termed 
metaplasia. 



CHAPTER V. 



SPECIFIC INFLAMMATIONS, OR INFECTIOUS GRANU- 
LATION TUMORS. 

These are peculiar forms of chronic inflammation, the exact 
position of which among pathologic processes was for a long time 
doubtful. They are classed among the inflammations because they 
give rise to tissues that are unfit for further use and have to be 
removed, and because the parablast is concerned in the removal. 
There is in all of them a leukocytic infiltration for the purpose of 
elimination, and likewise a tendency to regeneration, which, how- 
ever, as a rule, falls short of complete success ; sometimes a cure is 
achieved. 

The characteristic features of the specific inflammations are (a) 
a tendency to degeneration, (b) the absence, more or less complete, 
of blood-vessels, and (c) the tendency to form tumor-like masses. 

Various names have been given to these tumors : infectious 
granulation tumors or granulomata, because some consist of granu- 
lation tissue and resemble tumors in outline ; leukocytomata, be- 
cause they are characterized by a leukocytic infiltration and form 
tumor-like nodules ; and specific inflammations, for the reasons 
given. The last is the preferable designation. The most important 
specific inflammations are tuberculosis, syphilis, leprosy, glanders, 
and actinomycosis. 

TUBERCULOSIS. 

Tuberculosis comprises the morbid changes produced by the 
presence of the tubercle bacillus in the body. 

Historical. In the history of tuberculosis, the names of three 
men overshadow all others. These names are Laennec, Villemin ) 
and Koch. To Laennec (1837) we owe the discovery of the physical 
signs of pulmonary tuberculosis; to Villemin (1865), the demon- 
stration, by experiments upon lower animals, that tuberculosis is an 
infectious disease; and to Koch (1882), the immortal discovery of 
the cause, the bacillus tuberculosis. 

(66) 



TUBERCULOSIS. 67 

The disease affects man and the lower animals, especially horned 
cattle; somewhat less frequently, the monkey, guinea-pig, rabbit, 
dog, horse, sheep, and cat. Nearly all animals are susceptible to in- 
oculation, some, as the guinea-pig, rabbit, and field-mouse, suc- 
cumbing readily ; others, as the horse, dog, and cat, offering 
considerable resistance. 

Seats of the disease. The following organs, named in the order 
of frequency, are affected by the disease. 

1. The respiratory and intestinal tract. In the former the dis- 
ease attacks the lung substance proper, the bronchioles, and the 
larynx ; in the latter, the lower portion of the ileum, the mouth, 
throat, and rectum. 2. Lymphatic glands. 3. Serous membranes — 
peritoneum, pleura, meninges. Tuberculosis of the peritoneum is 
more often primary than that of the pleura, which is generally sec- 
ondary. 4. Bones. 5. Spleen. 6. Kidney. 7. Suprarenal capsules. 
8. Brain. 9. Middle ear. 10. Uterus and its appendages. 11. 
Testicle. 12. Bladder. 13. Skin. 

In the adult the lung is the most common seat of the disease ; 
in children, the lymphatic glands, serous membranes, and bones. 

The following organs and tissues are rarely affected : Salivary 
glands, thyroid gland, ovary, muscles, cartilage, and heart. 

Cause. — The Bacillus tuberculosis of Koch. The bacillus is 
the only cause of tuberculosis, and is always derived from a person 
or animal suffering from the disease. 

Tuberculosis is, therefore, contagious, and there is absolutely 
no ground for the contrary view maintained by some physicians. 
If we are sure of anything it is that in every case in which the ori- 
gin of the disease has been traced, it has been found to be another 
person or animal. 

The Bacillus. The bacillus is rod-shaped, slightly bent upon 
itself, 3 fi long, 0.2 /* in width, non- motile, and when stained fre- 
quently presents a beaded appearance. The beading has been sup- 
posed to be due to the presence of spores, but this has never been 
proved. More probably it is caused by the contraction and breaking 
up of the stainable portion, permitting us to see the empty spaces 
formed between the fragments and the outer membrane. It is 
believed that bacilli undergoing degeneration are those chiefly acted 
upon by the stain in this manner. The presence of the bacillus is 
readily demonstrated in the secretions and discharges, and in the 
tissues of the affected organs. 



68 NOTES ON PATHOLOGY. 

Special processes are required to stain the bacillus, all 
depending upon two peculiarities possessed by it: (i) It takes 
the stain with difficulty ; (2) after being stained it holds the stain 
tenaciously. 

In order to facilitate the staining certain substances are used as 
mordants. Carbolic acid, anilin oil, and the alkalies are thus em- 
ployed. Strong mineral acids and alcohol serve as differentiating 
agents, both being generally used. The stain may be applied to 
fluids and to tissues. For the rapid demonstration of bacilli in the 
latter, it is advisable to rub up a portion of the tissue in a mortar 
into a fine pulp and to treat it as sputum. 

For all practical purposes the best stain is that known as ZiehVs 
solution. It has the great advantage that it keeps indefinitely, while 
those made with gentian-violet and other dyes deteriorate with age. 

ZiehVs Solution: 

Fuchsin , 1 

Alcohol 10 

5 per cent watery sol. carbolic acid 90 

As a decolorizing agent and counterstain we employ Gabbefs 
solution. 

Methyl blue 1-2 

Sulphuric acid 25 

Water 1 . 75 

The bacilli appear as dark-red, almost black, rods on a blue 
field. 

Cultivation. This is more difficult than in the case of most 
other pathogenic microbes, and at first was only achieved on blood- 
serum. The serum is obtained from an animal, as a horse, and 
after decantation is placed into tubes and sterilized by heating for 
one hour on six successive days to 50 C. ; on the sixth day the 
temperature is raised to 6o° C. It is then placed into an incubator 
for twenty-four hours, and is finally heated to 68° C. By this pro- 
cess the serum becomes stiff, but the albumin is not coagulated. 

The bacillus also grows on agar or bouillon to which about six 
per-cent. of glycerin has been added. 

To secure the growth of the bacillus it is necessary (1) to keep 
the tube constantly at 37 ° C. ; (2) to avoid drying by too much 
ventilation ; (3) to eliminate the presence of other micro-organ- 
isms. 



TUBERCULOSIS. 69 

To obtain a pure culture, (a) A guinea-pig is inoculated with 
tuberculous material, and is killed in the third or fourth week of the 
disease, at a time when the morbid tissues are not yet breaking 
down. Under antiseptic precautions a lymphatic gland is removed, 
cut with a sterile knife, and the surface rubbed upon glycerin agar. 

(b) A pure culture may also be obtained directly from sputum 
in the following way : The patient disinfects his mouth and spits 
into sterile Petri dishes. A grayish-yellow nodule is taken up with 
sterile forceps, and carefully washed in several dishes of sterile 
water, and finally rubbed upon glycerin agar or introduced into 
glycerin bouillon. The repeated washing removes the contaminat- 
ing micro-organisms. 

Growth of the bacillus. The growth becomes visible in from 
seven to fourteen days, appearing first in the form of isolated, mi- 
nute, grayish-white scales. As a rule the growth does not proceed 
any further, and it is necessary to inoculate a second tube. Here 
the growth is more active, producing a grayish membrane rising 
somewhat above the surface. 

Under a low power (80 diameters) the bacilli are seen to arrange 
themselves in peculiar S-shaped curves. 

The tubercle bacillus does not lose its virulence except after 
having been grown for many generations. 

Morbid Anatomy. — The characteristic lesion of tuberculo- 
sis is a small nodule called the gray nodule or miliary tubercle. This 
is a small semi-translucent nodule, slightly elevated above the sur- 
rounding tissue, and somewhat harder, and varying in size from Y V 
to 2 mm. 

Miliary tubercles as a rule are present in large numbers, and are 
distributed, especially in parenchymatous organs, with some regu- 
larity, being about equidistant. On serous membrane they follow 
the course of the lymphatic vessels. 

Their outline is not sharp ; they merge into the surrounding 
tissue, cannot be peeled out, and are frequently surrounded by an 
inflammatory zone, which is always visible with the microscope. 
Quite often the grayish masses are opaque in the centre ; at times 
they present a yellowish tint. This indicates a cheesy change and 
is in direct proportion to the size of the nodule. 

Besides appearing as the miliary tubercle the disease occurs also 
in the form of the tuberculous infiltration, which is produced either 



70 NOTES ON PATHOLOGY. 

(a) by a coalescence of numerous tubercles or (b) by a peculi- 
arity in the cellular infiltration, which does not arrange itself in 
nodules, but infiltrates large areas, the size depending on the 
anatomic relations of the parts. In the lung an entire lobe may be 
affected. The larger the diseased mass, the greater the cheesy- 
degeneration. 

The tuberculous infiltration is formed in chronic processes, while 
miliary tubercles indicate acuteness. An exception is acute tuber- 
culous pneumonia, which is an acute, rapid, general tuberculous 
infiltration with a tendency to caseation. 

When the tuberculous infiltration is extensive the structure of 
the affected parts is lost, and is replaced by cheesy material, pale, 
yellowish or dirty-gray in color, dryer and harder than the sur- 
rounding tissue. This is known as the yellow tubercle. 

The changes in tuberculous areas depend somewhat upon the 
animal affected, and also upon the organ involved. In general the 
lesions show a tendency to degenerate. They break down by lique- 
faction necrosis, with the formation of ulcers — tuberculous ulcers — 
or cavities. 

These cavities (vomica) are most common in the lung, and are 
apt to become infected with the micro-organisms of suppuration, 
which assist in the destructive process. Cavities not communica- 
ting with the external air are seen in connection with bone disease, 
and are termed cold abscesses (psoas, vertebral, hip-joint abscess). 
The contents of these abscesses is as a rule not purulent, but may 
be from mixed infection, or, rarely, from a pyogenic activity unfolded 
by the tubercle bacillus itself. 

At times there is in tuberculous lesions a tendency to regener- 
ation, the result being the encapsulation of the lesion or the com- 
plete healing with removal of the diseased 
!fe^i %£® structures and their replacement by a scar. 
(b) Microscopy. The essential feature ot 
the tuberculous process is a group of con- 
nective tissue cells lying closely together. 
These cells possess a vesicular nucleus and 

S^^S^f^^ a comparatively large amount of protoplasm, 
&%*$&i%&f*» an d are known as epithelioidal cells. Fre- 
Tubercie. quently the nuclei stain imperfectly. The 

characteristic picture of the tubercle is completed by the appear- 
ance, in the center, of a giant cell, and at the periphery, around the 




TUBERCULOSIS. 7* 

epithelioidal cells, of a group of round cells of leukocytic origin, 
the so-called lymphoid cells. 

It is not necessary that these three kinds of cells should always 
be present together, but when associated they constitute the typical 
tubercle. The giant cell may be absent and the round cells may 
form an unimportant part of the picture, but the epithelioidal cells 
are an invariable feature, since they are the first evidence of the 
presence of the bacillus. 

The epithelioidal cells show no tendency to form connective 
tissue, but remain indolent, their protoplasm becoming granular and 
even fatty. The formation of the giant cell is an evidence of de- 
generation. It seems as if the irritant gave rise to a multiplication 
of nuclei, but that something prevented the division of the proto- 
plasm. The appearance of the giant cell in the tubercle is the same 
as in other conditions — it is a large, irregular protoplasmic mass, 
8-200 u in diameter, with a large number of nuclei. These are 
vesicular, like those of the epithelioidal cells, and are arranged 
either around the periphery or toward one pole of the cell. 

The degeneration begins in the giant cell, and is a form of coagu- 
lation necrosis, but not a fibrin formation ; in appearance it resem- 
bles amyloid. The degenerated portion does not stain. Frequently 
the central cells, the giant cell and epithelioidal .._ 
cells fuse and together undergo degeneration, g 
In this way a large degenerated mass is pro- J^ 4< ' ^ *V>> 
duced, with giant cells and epithelioidal cells ^^Sf| \ 



at the periphery, the whole being surrounded 

by a leukocytic infiltration. The structureless SPi^ 

center with the wreath-like accumulation of cheesy Tubercle. 

nuclei at the periphery has been aptly compared to a " raked field " 

(Professor Guiteras). Considerable debris and pigment are present 

in the degenerated area, particularly toward the periphery — in the 

lung this pigment is in part coal-dust, in part it is of obscure origin. 

The structures that have undergone coagulation necrosis very 
soon become the seat of fatty degeneration. By the union of these 
two degenerative processes — coagulation necrosis and fatty degen- 
eration — the picture of cheesy necrosis is produced. 

Fate of the fibrillar intercellidar substance. This participates 
in the degenerative changes, but at times is preserved for a some- 
what longer period than usual, in which case it holds the cells 
in a fine fibrillar reticulum. This constitutes the reticulated tubercle. 




72 NOTES ON PATHOLOGY. 

In some tubercles the round cells so predominate as to conceal 
even the epithelioidal cells. Such tubercles resemble lymphatic 
glands and are known as lymphoid tubercles. They are not rare 
in the mucosa of the intestines. 

Position of the bacillus. In the early stages the bacilli are 
found between the epithelioidal cells, rarely within them. Later 
they occur in largest numbers in the giant-cell, occupying a position 
just within or among the nuclei ; rarely one is seen in the degenera- 
ted portion. Eventually, the bacilli are found in the epithelioidal 
cells, and among and within the leukocytes. 

Although some of the epithelioidal cells are derived from the 
endothelial cells of blood-vessels, they show no tendency to form 
new blood-vessels, a fact that in a large measure accounts for the 
degeneration in the tubercle. At times there is a more or less 
successful effort at regeneration. 

Sources of the cells in the miliary tubercle, (a) The leuko- 
cytes come from the blood-vessels, (b) The epithelioidal cells are 
derived (i) from pre-existing connective tissue cells; (2) from endo- 
thelial cells ; (3) from epithelial cells, (c) The giant-cell originates 
from epithelioidal cells. 

Localities in which giant-cells are found. Besides in the 
tubercle, giant-cells occur (1) where bone is being absorbed (physi- 
ologic); (2) in the placental site of the uterus ; (3) about foreign 
bodies; (4) in the air-vesicles in pneumonia; (5) in syphilitic 
gumma ; (6) in syphilitic endarteritis ; (7) in granulating wounds 
healing slowly ; (8) in giant-cell sarcoma, and (9) in actinomycosis. 

Pathogenesis Of Tuberculosis. — Tuberculosis is at first a 
local disease, and may remain so indefinitely. In the center of the 
affected structures we find an area of cheesy or liquefaction necrosis, 
and surrounding it a grayish zone of cellular infiltration, through 
which miliary tubercles are scattered. It is through the gradual 
extension of these miliary tubercles that the neighboring and adja- 
cent tissues are invaded. This mode of spreading is spoken of as 
extension by continuity or contiguity. But the disease is still a local 
process. Local tuberculosis is also termed primary tuberculosis. 

Secondary tuberculosis is produced (a) by extension along the 
lymphatic channels. This is well shown in tuberculosis of the mu- 
cous membrane of the intestines, in which we find miliary tubercles 
along the lymphatic vessels of the peritoneum, or we may find the 



TUBERCULOSIS. 73 

mesenteric glands tuberculous, with or without involvement of the 
lymphatic vessels. (b) By extension along the normal (open) chan- 
nels, with the material carried along these channels, viz.: along the 
respiratory and intestinal tracts, (c) By extension along the blood- 
vessels, with the blood. The resulting tuberculosis is apt to be 
general and very acute. 

The relation between the secondary and primary tuberculosis is 
as a rule readily traced ; but in tuberculosis of the lymph glands we 
may not find any disease of the rootlets. In such cases we are forced 
to assume that either (i) the bacilli enter through the surface, as 
e. g., the mucous membrane of the intestines, and cause disease in 
the lymphatic glands, without producing any recognizable lesion at 
the point of entrance ; or (2) that there is a latent tuberculosis, i. e., 
the bacilli enter the fetus in utero and develop at a variable period 
after birth. Both explanations are acceptable ; they probably 
account for different cases. 

Modes of Infection. — (a) By inhalation, which is the most 
common mode of infection in the human subject. The tubercle 
bacilli are contained in the air. This has been clearly proved in the 
experiments of Cornet, who found by exposing pans in the wards 
of hospitals, collecting the dust that was deposited, and introducing 
it into guinea-pigs, that the animals inoculated with dust from 
wards containing tuberculous patients died of tuberculosis. The 
presence of bacilli in dust results from the drying and pulverization 
of the sputum. Sputum in the moist condition does not contami- 
nate the air. 

(b) By the food, especially by the milk of tuberculous cows 
the udders of which are affected, and by the meat of tuberculous 
animals. Infection from milk is more common in children than in 
adults. Thorough cooking of the food destroys the bacilli, but the 
methods of smoking and curing meat as generally applied are 
insufficient for the destruction of the micro-organisms. 

(c) By direct inoculation. This is an infrequent mode of infec- 
tion. It gives rise to a local tuberculosis, which may after a time 
become generalized. Examples are the anatomical wart, and the 
tuberculosis of the penis, that in a few instances has followed the 
rite of circumcision. 

(d) By hereditary transmission. The transmission of the 
tubercle bacillus to the offspring is possible, as instances oi 



74 NOTES ON PATHOLOGY. 

tuberculosis of the fetus have been recorded, but the occurrence 
is rare. In such cases the bacilli usually pass through the placenta 
from the mother to the fetus ; their transmission by means of the 
semen is possible, but must be exceedingly infrequent. 

As the majority of cases of tuberculosis occur after the first 
year of life, it is highly probable that infection is most frequently 
post-natal. Nevertheless, we must recognize an hereditary tendency 
or predisposition to the disease. Certain families are more suscep- 
tible than others just as guinea-pigs succumb more readily than 
other animals. This predisposition is assumed to depend on a faulty 
condition of the body -juices. The so-called " signs " which for- 
merly were supposed to indicate a predisposition to phthisis, and 
which collectively were termed " scrofulous diathesis," in reality 
indicate the existence of the actual disease : scrofulosis in the 
majority of instances is tuberculosis. 

Many of the early manifestations of tuberculosis in children 
are curable ; indeed, complete healing may occur at any period ot 
life. 

Tuberculosis in children affects most commonly the lymphatic 
glands, the bones, and the meninges ; in adults, the lungs, the other 
manifestations being secondary to the pulmonary infection. 

Local and general effects of the tubercle bacillus. 

(a) Local action, (i) The bacillus exerts a marked chemo- 
tactic action, the chemotactic substance being an integral part ot 
it and not a product of its life activity. This fact has been 
demonstrated by Prudden who obtained the same round cell 
infiltration by the injection of dead tubercle bacilli as is produced 
by living bacilli. 

(2) The bacillus has a tendency to cause special forms ot 
degeneration — caseous and liquefaction necrosis. In many instances 
the liquefaction necrosis is due to mixed infection, especially the 
entrance of pyogenic micro-organisms. But the tubercle bacillus 
alone is also capable of inducing suppuration, as is seen in some 
cold abscesses. 

(b) General effects. These may consist (1) in a local or general 
outburst of miliary tubercles, the dissemination taking place through 
the blood-current, or (2) in a cachexia. This is to some extent 
due to the circulation of toxic compounds elaborated by the 
tubercle bacilli. Mixed infection is, however, an important factor 
in the production of the cachexia, and in the majority of cases a 



TUBERCULOSIS. 75 

septicemia develops from toxins originated by pyogenic micro- 
organisms. Advanced stages of cachexia are often associated with 
an amyloid change in many organs. 

The frequent injection of tuberculin is also capable of bringing 
about a cachectic state. 

Tuberculosis in the Lower Animals. 

{a) In cattle. Two forms of the disease occur ; (i) that of the 
serous membranes, and (2) that of the parenchymatous organs. 

(1) The tuberculosis of serous membranes, the so-called "pearl- 
disease," assumes the form of pendulous or sessile conglomerate 
masses, occurring in the pleura or peritoneum. The histologic 
features are, in the main, the same as those of tuberculosis in man, 
but there is a larger amount of fibrous tissue, which accounts for 
the ability of the masses to hold together, and there is also, together 
with cheesy necrosis, a marked tendency to calcification. 

(2) In parenchymatous tuberculosis we find the same tendency 
to cheesy degeneration and cavity formation as in the human being, 
but it is generally associated with calcification. 

Not rarely in cows the udder is tuberculous, in that case the 
milk necessarily contains tubercle bacilli, although they are not 
easily demonstrated. Whether the milk of tuberculous cows, the 
udders of which are not affected, contains the bacilli, has not been 
positively proved. Milk is a frequent source of infection (though 
by no means as frequent as the inhaled dust), and tuberculosis is 
more common in localities where milk is largely used as a food. 

Certain breeds of cattle, especially the deep milkers, as, e. g, 
the channel breeds, are eminently prone to tuberculosis. 

(b) In horses, the pleural and peritoneal cavities are especially 
involved, the process giving rise to pendulous masses resembling 
lympho-sarcomata. Calcification is not as marked as in bovine tu- 
berculosis. Infection is most common through the intestinal tract. 

(c) In sheep tuberculosis is rare, but can be produced experi- 
mentally. 

(d) In dogs and cats it is not frequent, although more common 
than in sheep. 

(e) In the hog the disease affects first the digestive tract, later 
the respiratory organs. There is in this animal a strong tendency 
to connective tissue formation. 

(/) In fowls tuberculosis of the digestive tract, particularly 
of the liver, is not rare. 



76 NOTES ON PATHOLOGY. 

(g) In rabbits and guinea-pigs. Both are very susceptible to 
the disease. In the lung the lesions in both animals are the 
same : multiple small cavities ; in the abdomen there is a striking- 
difference. In the rabbit, tuberculosis of the liver and spleen is 
miliary ; in the guinea-pig, the process is more extensive, involving 
larger areas and giving to the liver and spleen a marbled appear- 
ance, from the presence of the yellowish tuberculous areas in the 
reddish tissue of these organs. 

Course of tuberculosis produced experimentally in the guinea-pig. 

Under antiseptic precautions an incision is made in the skin 
and the tuberculous material introduced into a pocket in the sub- 
cutaneous tissue. The wound heals rapidly. Toward the end ot 
the second week the nearest lymphatic glands enlarge, the wound 
becomes indurated, and soon reopens and discharges a flaky, puru- 
lent material ; gray tubercles become visible at the point of inocu- 
lation. In the third or fourth week general symptoms appear, fever, 
emaciation, rapid respiration. Death takes place in from four to 
eight weeks. 

In order to study the phenomena of local tuberculosis, step by 
step, the anterior chamber of the eye of a rabbit is inoculated. On 
the fifth day there will be found an accumulation of epithelioidal 
cells ; the tubercles on the iris become visible to the naked eye by 
the twelfth or fourteenth day. The process rapidly becomes 
general. 

SYPHILIS. 

Syphilis is a contagious disease, due to a specific micro-organ- 
ism, which up to the present has not been isolated. Lustgarten 
has discovered a bacillus in the lesions of syphilis, but its inocula- 
tion into animals in pure culture has failed to produce the disease. 

Syphilis presents three characteristic lesions : The hard 
chancre, the mucous patch, and the gumma. 

(a) The hard chancre or initial sclerosis. Though characteristic 
clinically, this cannot be differentiated from other inflammatory pro- 
cesses microscopically. It appears at the point of inoculation, 
usually the corona of the penis, two or three weeks after infection, 
as a papule the size of a split pea ; it has a tendency to ulcerate, 
the surface being covered with a layer of fibrin and discharging a 
serous fluid, which contains but few cellular elements. The lesion 
also becomes indurated from a peculiar coagulation necrosis of the 



SYPHILIS. 77 

intercellular substance of the deeper parts. In addition, there is a 
cellular infiltration of the walls of the blood-vessels, affecting chiefly 
the intima. This does not differ from the same process in other in- 
flammations, but is rather characteristic of all syphilitic lesions. The 
hyperplasia contributes to the hardness of the chancre. 

Microscopically, we find round cells and epithelioidal cells and 
sometimes giant-cells. 

The disease soon extends along the lymphatic vessels to the 
nearest lymphatic glands. The latter become enlarged, and consti- 
tute the indolent buboes of syphilis. 

The secondary lesions are the skin manifestations, the mucous 
patch, and the gumma. The skin eruptions are, as a rule, inflam- 
matory, and do not differ pathologically from similar affections due 
to other causes. 

The mucous patch and the gumma are the truly characteristic 
lesions of syphilis. 

The mucous patch or condyloma latum. This is a flat swelling, 
slightly elevated above the surrounding level, with an ulcerated sur- 
face, developing chiefly at the junction of skin and mucous mem- 
brane, as on the lip, anus, corona, and external genitals of the 
female. 

Microscopy. We have a marked round cell infiltration of the 
upper layers of the corium, causing an enlargement and elongation 
of the papillae. But this is not characteristic, since it occurs under 
other conditions. The peculiar features are the imbibition of the 
epithelial cells of the rete mucosum with fluid and their separation 
by this fluid. The upper layers of cells are thrown off in the 
discharge. 

The gummy tumor, or gumma. This, clinically a so-called t( 
lesion, is a rounded tumor with an indefi- 
nite outline varying in size from the size of 
a pea to that of a small apple. It is raised 
slightly above the surface and has a vari- 
able consistence, being at times harder, at 
times softer, than the surrounding tissue ; 
quite often the tumor becomes soft in the 
later stages. On section we find in the 
center a grayish or yellowish mass, Syphilitic gumma. 

" gummy " in appearance, whence the name. The gummy material 
occurs especially in the gummata of the bones and the skin, and 




78 NOTES ON PATHOLOGY. 

is due to a mucoid degeneration of the connective tissue. Solid 
gummy tumors are found chiefly in the viscera ; they are very rich 
in cells — epithelioid cells and round cells, and occasionally giant 
cells, particularly at the periphery. The last are not so abundant 
as in tuberculosis. In the center of these visceral gummata there 
are areas of fatty degeneration. 

There is in syphilis a marked tendency to the formation of 
connective tissue. Not only does this tissue form a capsule around 
the gumma, but new bands of fibrous tissue pass into the tumor, 
forming trabecular which separate islands of fatty material. In 
addition, bands of connective tissue extend in a radiating manner 
into the surrounding tissue. Upon this depends the peculiar stellate 
character of the scar remaining after the absorption of the gumma. 

Gummata situated on surfaces tend to break down by a process 
of suppuration, the resulting ulcer healing very slowly. In viscera 
absorption is most common, the scar being stellate. 

In connection with the gummy tumor as well as in other 
syphilitic processes we find a hyperplasia of the intima of blood- 
vessels, which is to a certain extent characteristic of the disease. 
It gives rise to thickening of the arteries, and also leads to a 
formation of new blood-vessels, a feature so strikingly deficient in 
tuberculosis. But even in syphilis the new sprouts tend to degen- 
erate, and the lesions, as the gumma, are insufficiently nourished. 

Seats of gummata. Gummata are found in the subcutaneous 
tissue ; in bones — especially the skull, tibia, and sternum ; in 
viscera, as the liver, testicle, spleen, brain, and, rarely, in lung and 
kidney. 

Hereditary Syphilis. — The following statements may be 
made concerning the transmissibility of syphilis : 

1. Syphilis is readily transmitted from the parents to the fetus.. 

2. The poison may pass through the placenta in either direction, 
i. e. y from mother to child, or vice versa. Syphilitic lesions may 
occur in the placenta, e. g. f condyloma of decidua. These are not 
the result of direct infection, but are the local manifestations of a. 
general disease. 

3. Most frequently the fetus is infected by the mother. 

4. The more recent the syphilitic manifestations in the mother 
before conception, the more apt is transmission to take place. 

6. A syphilitic father may beget a healthy or syphilitic child,, 
the latter without infecting the mother. 



GLANDERS. 79 

6. The syphilitic fetus may or may not inoculate the mother ; as 
a rule, it, the fetus, produces a profound impression upon the mother, 
since the latter shows a distinct immunity to syphilis. An 
actual infection of the mother does not take place, but the 
toxins of the disease enter her blood and stimulate the formation of 
the antitoxins. This seems to be proved by the failure of the 
mother to become inoculated from the sores in the infant's mouth 
(Colles' Law). 

7. The disease may be transmitted by the mother infected 
during pregnancy. 

Abortion is common in pregnant women suffering from syphilis. 
It is generally the result of syphilitic endometritis. 

Syphilitic children present frequently no outwardly manifesta- 
tions of the disease at birth, although on post-mortem examination, 
we find lesions in the skeleton. Distinct phenomena appear at the 
second or third month, and are either chronic fibroid processes in 
the lung, pancreas, and spleen, or gummata in the bones, liver 
spleen, and lung. 

GLANDERS. 

This is a contagious disease occurring ordinarily in horses and 
asses, but transmissible to man and most other mammalia. The 
guinea-pig and the field-mouse are particularly susceptible to 
experimental inoculation. 

The cause of the disease is the bacillus of glanders, or bacillus 
mallei, discovered by Loffler. It is about the same length as the 
tubercle bacillus, but broader and straighter; it is facultative 
anaerobic, motile, and occurs in groups forming angles, and usually 
lies between the cells. It does not stain by Gram's method, but 
is stainable with the ordinary anilin dyes. The best solution is 
carbol-methyl-blue. 

Methyl-blue, 1.5 

Alcohol, 10 

5 per-cent. watery sol. carbolic acid, 90 

This is allowed to act on the section for 10-30 minutes. For 
differentiation a weak solution of hydrochloric acid is employed. 

Hydrochloric acid, 10 drops. 

Water, 500 c.c. 

The section is then washed in water, placed on a slide, dried, . 
and mounted in Canada balsam. 



So NOTES ON PATHOLOGY. 

The bacillus grows readily on all alkaline media, but char- 
acteristically only on the potato. If the potato is kept at 37 C, 
we find in two or three days the development of amber-colored 
drops looking like beads of honey. The colonies gradually enlarge 
and grow darker. 

Morbid Anatomy. — There are two forms of glanders (a) 
that affecting the respiratory mucous membrane — glanders proper, 
and (b) that of the skin, subcutaneous tissue, and lymphatic glands. 
The latter is more chronic and is termed farcy. 

In the horse the disease appears most frequently in the nasal 
mucous membrane, and presents itself either in the form of distinct 
tumors or as a diffuse infiltration. The tumors vary in size from 
those just visible to the size of a cherry; they are slightly raised 
above the surface, are pearl-gray in color, and surrounded by an 
inflammatory zone. They either occur as isolated nodules or, as is 
more common, are aggregated in groups. The central portions are 
at first translucent, but rapidly become opaque and yellow. 

The nodules have a marked tendency to undergo fatty and 
puriform changes in the center, being eventually transformed into 
ulcers of varying size and depth. The ulceration frequently extends 
to the cartilages and produces a " honey-comb " appearance. 

In chronic cases there may be a tendency to healing with the 
formation of a puckered cicatrix. 

Nodules similar to those just described may occur in the lung ; 
they are here usually surrounded by areas of broncho-pneumonia. 
Abscesses are very apt to form both in the pneumonic patches and 
in the nodules. Apart from these manifestations the lung as well 
as other organs may be the seat of miliary or il embolic " glanders. 
We may also have, in the lungs, a general infiltration affecting a 
large area, and resembling a lobar pneumonia. It is, however, not 
a true pneumonia, but a specific infiltration similar to caseous tuber- 
culous pneumonia. The affected portions are more gelatinous and 
translucent in appearance than those of caseous pneumonia, they 
have a greater tendency to break down, and are very frequently 
the seat of hemorrhagic infiltration. 

The lymphatic glands become involved very early in glanders. 
The characteristic features of glanders, to be noted in performing 
autopsies, are (1) ulceration of the air-passages, (2) a tendency to a 
rapid breaking down and suppuration of the nodular masses. 



LEPROSY. 8.1 

Microscopy. Histologically, we find in glanders round cells 
and epithelioidal cells, and, as evidences of acute inflammation, the 
accumulation of multinuclear leukocytes. 

Farcy presents subcutaneous nodules of varying size, associated 
with a diffuse inflammation of the subcutaneous tissue and the inter- 
muscular septa, particularly of the lower extremities. The lesions 
are distinct nodules as well as inflamed lymphatic vessels and lymph- 
atic glands. Suppuration is the rule, and leads to the formation 
of deep, ragged-edged ulcers, which heal very slowly. 

Chronic glanders occurs either as isolated tumors along the 
lymphatic channels or on the mucous membranes, or as chronic, 
slowly-spreading ulcers. The latter may heal, the scars being 
usually stellate. 

The duration of glanders is from eight to twelve days to 
several years. 

Glanders in man. In man, glanders is an acute febrile disease 
of typhoid type, the local lesions being those of the respiratory 
mucous membrane and of the subcutaneous tissue, together with 
a diffuse pustular eruption. Lobular pneumonia is generally 
present, the consolidated areas being as a rule the seat of hemor- 
rhagic infiltration. 

In chronic glanders, we have the formation of nodules at differ- 
ent periods, or torpid ulcers on the skin and mucous membranes. 
The points of accidental inoculation in man are the conjunctiva, 
the nose, and the skin. 

LEPROSY. 

Leprosy is a chronic infectious disease due to the bacillus 
lepra?. 

It affects especially the skin and the peripheral nerves, and 
leads to great deformity, to ulceration, and to disturbances of 
sensation. 

Some obscure forms of nervous disease, associated with altera- 
tions in the peripheral nervous system (anesthesias, etc.), are said 
to be due to leprosy. 

There are a number of foci of leprosy in the United States, 
the most important being those of the Pacific coast, Louisiana (near 
New Orleans), Florida, and South Carolina (near Charleston). The 
disease shows a tendency to increase, especially in Europe. 



82 NOTES ON PATHOLOGY. 

ACTINOMYCOSIS. 

This is a contagious disease, affecting especially the mouth of 
horned cattle and pigs. It is caused by a micro-organism, the actino- 
myces, the position of which has not been definitely settled, though 
it is generally described as a cladothorix form of bacterium. 

The micro-organisms are club-shaped, and are grouped in the 
form of rosettes, the club-ends being at the periphery, while the 
center is made up of a mass of fine filaments. The latter are the 
active living elements, while the club-ends are dead, the clubbing 
being an evidence of degeneration. The spores are found in the 
center, among the filaments ; they are spherical in shape, resembling 
micrococci. The rosettes vary in size, from 40 to 50^ to 1 or 2 mm.; 
the larger ones are visible to the naked eye, being either grayish 
like fragments of mucus, or yellow. The yellow granules are par- 
ticularly striking ; they float in the pus, and are generally the first 
objects to attract attention. 

Morbid Anatomy. — (a) Macroscopy. In cattle, the disease 
is usually circumscribed to the lower, at times also to the upper 
jaw, and gives rise to the formation of nodular tumors. The growth 
begins in the submucous tissue, and extends to the 
periosteum and even to the bone. Suppuration 
occurs in the form of innumerable small abscesses, 
the rupture of which leads to a peculiar honey-comb 
appearance. Frequently there is a successful attempt 
Actinomyces a t connective tissue formation, resulting in the 
development of large tumors about the jaws (Jzimpy jazv), commonly 
with a degenerated center. 

(b) Microscopy. The rosettes are found in the midst of granu- 
lation tissue made up of epithelioidal cells and sometimes giant- 
cells. Suppuration is the rule ; exceptionally, abundant connective 
tissue is formed. 

The seats of the disease in cattle are the jaws, tongue, and sub- 
maxillary glands. Although generally circumscribed to these 
places, it may extend to the respiratory and alimentary tracts. 

In man the disease presents the same characters as in cattle. 

Pathogenesis. — The micro-organism is introduced with the 
food, especially with grains, such as barley and wheat. These 




ACTINOMYCOSIS. S3 

grains penetrate the mucous membrane and carry the fungus with 
them. They have been found in the mucous membrane of the 
mouth and in the tonsils. 

Cultivation. The actinomyces can be grown on the ordinary 
media, glycerin-agar being especially adapted. 

Staining. The most striking appearance is produced by picro- 
carmin, which stains the actinomyces yellow and the granulation 
tissue red. Gram's method also yields good results ; A it is advisable 
to use a preliminary carmin stain. 



1 



CHAPTER VI. 



TUMORS. 



Tumors are hyperplasias which, though presenting no new 
cells, i. e., none the counterpart of which cannot be found in the 
body at some time of its development, yet have certain peculiarities 
which separate them from other hyperplasias. These peculiarities 
are: 

1. They change the configuration of the part in which they 
develop. 

2. Their tissue differs from that of the surrounding parts. 

3. The tumor-growth is persistent and progressive. 

4. Tumors have a special blood-supply. 

5. The hyperplasia has no apparent cause or object. 

6. The tissue is generally embryonal in character, either in 
part or throughout. 

7. Tumors are malignant — they give rise to metastasis, and 
recur after removal. 

8. They tend to degenerate. 

Tumors are said to be heterotopic growths because they are 
found in places where the tissue of which they are composed should 
not exist ; heterochronies because the tissue occurs at a time when it 
should not be found in the body ; tumors may also be produced by 
the excessive growth of a tissue in places where it is usually present 
in small quantity. 

Pathogenesis Of Tumors. — The true causes of tumors are 
not known, but several theories have been advanced to explain 
their development. 

I. The theory of tumor diathesis (Billroth), which assumes the 
existence of peculiar predisposition, inherited or acquired, to the 
development of tumors. This theory has very little value. 

2. The mechanical theory (Virchow). According to this certain 
tumors are due to injuries. In a sense this is true, but the same 
injuries do not cause tumors in all individuals ; moreover, many of 
the so-called tumors following injuries, are really inflammatory 
hyperplasias. 

(84) 



FIBROMA. 85 

3. The embryonal or evolutional theory (Cohnheim). This 
ascribes the origin of tumors to errors of development during em- 
bryonal life ; some portions of tissues are misplaced, and afterwards 
taking on active growth, become tumors. This theory accounts 
satisfactorily for a certain class of new growths, particularly the so- 
called mixed tumors and the dermoid cysts. 

4. The nervous theory. It is assumed that tumors may be due 
to disturbances in the trophic functions of the nervous system. This 
is probably true in some cases. 

5. The parasitic theory. The development and course of many 
tumors could be best explained on this theory, but unfortunately 
the parasites have not yet been found. 

Classification Of Tumors. — 1. Parablastomata — Pan- 
blastic, or connective tissue tumors. 

2. Archiblastomata — Archiblastic tumors. 

3. Teratomata — Complicated tumors, the result of errors* 

of development. 



PARABLASTOMATA. 

FIBROMA. 

This is a non-malignant tumor of slow growth, consisting of 
fibrous tissue. There are two varieties, the hard and the soft 
fibroma. 

[a) Hard fibroma. This is a firm, nodular, well circumscribed 
tumor, surrounded by a capsule and present- ^g^^^^m^-^^^L 
ing on the surface of section a white, glistening 
appearance and striae indicating the direction 
of the fibers. It may be single or, as is usual 
in the skin, multiple. 

Microscopy. It consists of fibrous tissue 
poor in cells, being chiefly made up of a dense Hard Flbroma - 

fibrillar intercellular substance. Blood-vessels are few in number, 
unless the tumor has undergone telangiectatic change. The fibrous 
bundles may be disposed regularly, in layers, or irregularly. 

Seats. These are the skin, fasciae, tendons, periosteum, uterus, 
along nerves, rectum, and mammary gland. 





86 NOTES ON PATHOLOGY. 

(b) Soft fibroma. This is a soft tumor with a moist surface of 
section ; it is usually not as clearly circumscribed as the hard ; it 
may be single or multiple, polypoid or sessile. 

Microscopy. We find a large number of 

cells ; the fibrillar intercellular substance does 

not run in distinct bundles, but forms a loose 

network resembling areolar tissue, differing, 

jS2^> however, in its greater richness in cells. 

Seats. These are the subcutaneous and 
submucous connective tissues, periosteum, inter- 

soft Fibroma. muscular septa, retro-peritoneal connective tissue, 
and along the course of nerves. The fibroma of nerves is known 
as false neuroma. 

Fibroma molluscum is a soft fibroma developing in the course 
of the fine nerve fibers of the skin and subcutaneous tissue. It is 
multiple. 

Papillomatous fibroma (wart). In this there is a great over- 
growth of the connective tissue in the shape of papillary excres- 
cences. They are covered by epithelium, which is also hypertrophied, 
but this is a secondary feature. If the same process occurs in 
glands, an adeno-fibroma is produced. 

There is no sharp line of separation between these fibromata and 
certain epithelial growths, although in some cases, as in the examples 
cited above, the fibrous tissue is clearly primarily hyperplastic. 

Combinations. Fibroma combines with myoma, lipoma, myx- 
oma, and sarcoma. 

Degenerations. These are calcareous infiltration, fatty infiltra- 
tion, mucoid degeneration, and telangiectatic or cavernous change. 

There are several conditions that have been described as 
fibromatous, which in reality are inflammatory processes — [a) Ex- 
tensive thickening of the serous membranes. We may look upon these 
as inflammatory, (b) Elephantiasis. This is characterized in part 
by a great overgrowth of the fibrous tissue, especially of the 
lower extremities, the cause of which is a chronic irritative obstruc- 
tion of the lymphatic vessels. There is also dilatation of these 
vessels. Analogous changes are met with in the scrotum and 
labium, which here must be considered as true tumors, since no 
cause has been discovered, (c) Keloid tumor. This is also an inflam- 
matory hyperplasia — an overgrowth of a scar ; it is most common 
in the colored race. 



GLIOMA. 87 



MYXOMA. 



This is a parablastic tumor after the type of the jelly of Whar- 
ton or the vitrous humor of the eye. 

(a) Macroscopy. It is a rounded, lobular tumor, frequently encap- 
sulated, consisting of a jelly-like substance traversed by fibrous 
partitions. The consistency varies with the extent of the mucoid 
change in the intercellular substance ; at times the tumor is quite 
hard, at others it is soft and contains mucoid cysts. The tumor may 
be congenital. 

(b) Microscopy. We find large numbers of stellate connective 
tissue cells, at considerable distances from each other, the inter- 
spaces being filled with a mucoid intercellular substance. The 
mucoid material gives the reactions of mucin. 

Seats. The loose subcutaneous tissue, especially of the back, 
about the umbilicus, the cheeks, the labia, the scrotum, and the 
axilla ; also in the membranes of the brain and cord, along nerves, 
in the mammary gland, and in the uterus. 

In the mammary gland the myxoma occurs both combined 
with other tumors and as a pure myxoma. The latter is peculiar 
in that it affects both glands and gives rise to an enormous, uniform, 
symmetrical enlargement of the breasts, a condition formerly termed 
hypertrophy. In the uterus myxoma develops in the villi of the 
chorion, and is known as the hydatidiform mole. It has a tendency 
to involve the uterine wall, and to recur after removal. 

Combinations. Myxoma combines with lipoma, fibroma, and 
chondroma. 

Degenerations. There may be complete myxomatous degen- 
eration, with cystic formation ; cavernous and telangiectatic changes 
also occur. 

Myxomas are, as a rule, benign, the hydatidiform mole being 
an exception. 

GLIOMA. 

This is a tumor consisting principally of neurogliar tissue. 

Macroscopy. The tumor is of moderate size, not encapsulated, 
and is at times not easily distinguished from the surrounding tissues, 
being quite similar to the gray matter of the brain. As a rule it 
produces in the brain a slight projection on the surface ; is usually 
reddish in color, and presents minute hemorrhages ; it is generally 



ss 



NOTES ON PATHOLOGY. 




Glioma. 



also a little harder than brain-substance, and its tissue appears some-r 
what gelatinous. The tumors are single, of slow growth, non- 
metastatic, but scarcely benign on account of their seat. 

Microscopy. We find a dense aggregation 
of neuroglia cells (Deiter's cells), which have a 
large nucleus and a small amount of protoplasm, 
and fine filaments extending in all directions. 
These filaments form an intricate network, which 
is best seen in teased preparations. The bloods 
vessels are often telangiectatic ; sometimes hemor- 
rhages are present. 
Seats. These are the brain, spinal cord, retina, suprarenal cap- 
sules, nerves and kidney. 

Combinations. The glioma combines with fibroma, myxoma, 
neuroma, and sarcoma. The combination with neuroma occurs in 

the nerve centers and consists in the pres- 
ence of ganglion cells in the neuroglial* 
tissue — ganglionar neuroglioma. They are 
rare. Glio-sarcoma most commonly grows 
from the granular layer of the retina, and is 
malignant on account of the presence of 
sarcomatous tissue. It is rare in the brain. 
These are calcareous, myxomatous, and fatty; 




Gangii nar N uroglioma. 

Degenerations. 



hemorrhages are common, and may lead to softening and to cystic 
formation ; cysts may also arise independently of hemorrhages. 

LIPOMA. 

This consists of fatty tissue. 

Macroscopy. Lipomata are rounded, lobulated, encapsulated 
tumors, that can be peeled out ; they are usually single, sessile or 
pendulous, and vary in size, being sometimes very large. Their 
consistency varies also, and depends on the amount of connective 
tissue and the extent of mucoid change. They are benign ; in 
some cases a hereditary predisposition is traceable. 

Microscopy. The tumor consists of lobules of fat, which are 
larger than in normal fat, and are enclosed in more prominent con- 
nective tissue trabeculae. 

Seats. The subcutaneous connective tissue, especially on the 
dorsum of the body — neck, shoulders, gluteal region ; also in the 



CHONDROMA. 89 

submucous and subserous tissue of the gastro-intestinal tract, where 
they are usually multiple. 

Combinations. Lipoma combines with fibroma and with 
myxoma. 

Degenerations. These are calcareous and myxomatous ; the 
latter may lead to the formation of cysts ; inflammation occurs as 
the result of injuries in the large lipomata, the blood supply of 
which is often defective — the tumors may ulcerate and break down. 

Lipoma in the lower animals. It is quite common, especially 
in horses, in which it grows from the subserous tissue of the perito- 
neum, and at times causes strangulation of the bowels. The lipoma 
in the lower animals presents the fat which is characteristic of the 
species — chiefly olein in the horse, stearin in cattle. 

CHONDROMA. 

This is a tumor after the type of cartilage. 

Macroscopy. They are well circumscribed nodular tumors, of 
considerable size ; usually hard, but sometimes soft from mucoid 
change. They are frequently multiple, espe- 
cially when growing from the hands and feet ; 
elsewhere they are generally single. In young j 
persons they are not rarely congenital. 

Microscopy. There are two varieties, the 
hyaline and the fibrous chondroma. The former 
arises from the skeleton, the latter is found in chonoroma. 

the internal organs. Histologically, the structure of chondroma 
differs from normal cartilage in the presence of cells irregular in 
shape and in grouping, and of bands of fibrous tissue. The cells 
are often spindle-shaped and stellate and some are devoid of 
a capsule; but normal cells are also present. 

Chondromas are benign, although cases of metastasis to the 
lung have occurred. 

Seats. Chondromas are found in the skeleton, springing from 
the bone or the cartilage ; in the lungs, growing from the bronchial 
cartilages ; in the parotid gland and in the testicle. In the last two 
organs they are " mixed tumors." Chondroma springing from bone 
may develop from the periosteum or the medulla of the bone. The 
multiple tumors of the hands and feet as a rule arise from the 
medulla. 




90 NOTES ON PATHOLOGY. 

Degenerations. These are mucoid, which may lead to cyst 
formation; fatty and calcareous. Calcification may be simple or a 
true ossification. 

Combinations. Chondromas combine with osteoma, fibroma, 
myxoma, and sarcoma. The chondro-sarcoma is malignant. The 
mixed chondroma (usually a chondro-sarcoma) of the parotid gland 
and of the testicle, is as a rule congenital ; its formation is explicable 
on Cohnheim's theory. 

In the lower animals, chondroma is found on the sternum and 
ribs, especially in the horse. The mammary gland of the dog is at 
times the seat of a mixed chondroma. 



OSTEOMA. 

This is a tumor after the type of bone. 

Many inflammatory bony formations assume the form of 
tumors — they have received the general name of hyperostoses. 
When dendritic they are called osteophytes ; when dense, exostoses. 
They are common about joints. 

True osteomata are often congenital, and are then symmetrical 
in their distribution ; at times an hereditary tendency exists — all 
these features show that they are true tumors. They are smooth, 
of considerable size, harder, more regular and slower in growth 
than chondromata, and well-encapsulated. 

Histologically, three varieties are distinguishable : (a) the hard 
or osteoma durum; (J?) the spongy or cancellated, or osteoma 
spongiosum, and (c) the medullary, i. e., one possessing medullary 
cavities, osteoma medullare. In osteoma the arrangement of the 
Haversian canals is similar to but not as regular as in normal bone. 
Osteoma is benign. It may be multiple when growing on the 
extremities. 

Seats. The skeleton, especially the bones, also the cartilages ; 
the pleura and the dura — in these the tumors assume the form of 
plates, particularly in the falx cerebri ; in viscera, as in the brain 
and lung. 

In the lower animals the inflammatory bony outgrowths are 
common, e. g., the spavin of horses. True osteoma occurs in the 
jaws of cattle, and in the horse, growing from the bones of the 
skull into the cranial cavity and into the nasal chambers. 







ANGIOMA (HEMANGIOMA). 91 

ANGIOMA (HEMANGIOMA.) 

This is a tumor consisting mainly of blood-vesssels. It is also 
known as erectile tumor. 

There are two varieties — the telangiectatic and the cavernous. 
(a) The telangiectatic angioma consists of dilated loops of capilla- 
ries and small veins. The walls have all 
the characters of those of normal vessels, 
but the connective tissue may be thick- 
ened. They are benign and usually con- 
genital. 

Seats. They occur on the skin, 
where they constitute the mother's 
marks, naevi, etc. ; in internal organs, Telangiectatic Angioma, 

as the brain ; in bones ; they are rare in mucous membranes. 

(b) The cavernous angioma consists of blood-spaces formed by 
trabecular of connective tissue, and lined by endothelium. Its 
type is the cavernous tissue of the penis. They are small, well 
circumscribed tumors, dark in color, not raised above the surface, 
with a distinct capsule, and are either single or multiple. 

Seats. It is most frequent in the liver of old people, but oc- 
curs also in the spleen, kidney, orbit, and bones. That of the liver 
may be injected from any system of vessels of the organ. 

Most visceral angiomata are cavernous. 

Degenerations. Angiomata are not subject to any peculiar de- 
generation, but hemorrhages may occur into the tumors from 
rupture of vessels. 

Combinations. They may be combined with fibroma or lipoma, 
but under such circumstances it is a difficult matter to decide 
whether the tumor was originally a fibroma or lipoma that has 
undergone telangiectatic change, or whether it was an angioma, in 
the walls of which an excess of fibrous or adipose tissue has de- 
veloped. Sarcoma is also frequently combined with angioma. 

LYMPHANGIOMA. 

This is a tumor consisting of dilated lymphatic vessels. 

There are two varieties — the telangiectatic and the cavernous ; 
these are not sharply differentiated, and generally occur together. 
They are most frequently found as congenital tumors, about the 
tongue (niacroglossid) and the lips and cheeks (macrochilia), and at 



92 NOTES ON PATHOLOGY. 

first sight appear as hypertrophies. Macroglossia is common in 
cretinism. A similar tumor is also found about the neck {hygroma). 

These forms of lymphangioma are readily accounted for on 
the theory of Cohnheim. 

Lymphangiomatous formations are also produced by obstruc- 
tion of the lymphatic channels — these can scarcely be called 
tumors, but are frequently parasitic diseases, as, e. g. } elephantiasis, 
which is due to the Filaria sanguinis hominis. In elephantiasis we 
have, in addition to the dilatation of the lymphatic vessels, a 
hyperplasia of the skin and subcutaneous tissue. At times the 
lymphangiomatous formation is circumscribed, particularly to the 
scrotum or labium — as it is difficult in these cases to discover a 
cause, the condition is classed as a true tumor. 

SARCOMA. 

Sarcomas are tumors composed of embiyonal tissue. They 
may be defined as connective tissue tumors in which the cells so 
predominate in number or size, that the intercellular substance be- 
comes a subordinate element. In ordinary connective tissue the 
intercellular substance constitutes the prominent feature, the one 
upon which the differentiation of the various kinds depends ; in 
sarcoma it fails to assume any of the types of adult connective 
tissue, and the differentiation is based on the character of the 
cells. There is at times, in sarcoma, a tendency to a better develop- 
ment of the intercellular substance, but the latter never becomes 
prominent. 

The Characteristics of Sarcoma. — i. Origin and mode of 
growth. Sarcomas arise either from healthy connective tissue 
(which is most common), or from connective tissue showing a ten- 
dency to hyperplasia. Growth occurs in one of two ways : (a) by 
proliferation of the sarcoma cells, or (b) by metaplasia, i. e., by the 
conversion of the surrounding tissues into sarcoma. 

2. Rapidity of growth. The growth of sarcoma is rapid, espe- 
cially in the small-celled forms, and, as in all rapidly growing 
neoplasms, the tumor is apt to be circumscribed, although usually 
not encapsulated. Carcinoma on the other hand always infiltrates. 

3. Blood supply. This is abundant. We find normal blood- 
vessels as well as, and this is characteristic, blood-vessels without 
parietes, the sarcoma cells forming the walls. The endothelial 



SARCOMA. 93 

lining is always present. In many sarcomas the growth occurs 
along the walls of well-formed blood-vessels. 

4. Consistency and color. These vary with the richness in 
cells, the amount of pigment, and the abundance of blood-vessels. 
As a rule sarcomas resemble brain matter. The small-celled 
forms are soft; in some the intercellular substance is ossified — such 
tumors are hard. It is a general rule that the softer tumors the 
more malignant, but there are two striking exceptions : the perios- 
teal sarcoma is very hard, yet highly malignant, while the myxo- 
sarcoma is quite soft, yet comparatively benign. 

5. Degenerations. These are (a) fatty and cheesy change, (b) 
calcification, (c) ossification, (d) inflammation which may lead to 
superficial ulceration (that of carcinoma is deep) ; the granulation 
tissue at times forming fungous masses ; (e) cystic change — cysts 
may be due to softening, or to retention of secretion from pressure 
on gland ducts, this giving rise to the adeno-sarcoma and, when the 
dilated ducts are large, to the cyst-adeno-sarcoma ; or they may be 
due to extravasation ; (/) telangiectasis, which often leads to 
thrombosis ; (g) hemorrhages into the tumor. 

6. Seats. These are, in the order of frequency, the skin and 
subcutaneous tissue, inter-muscular septa, subserous connective 
tissue, eye, and periosteum of long bones. Less frequently, we find 
sarcomas in the interior of bone, in lymphatic glands, nerve sheaths, 
adventitia of blood-vessels, and membranes of brain and cord. 
They are rare in mucous membranes, especially of the uterus and 
bronchial tubes ; in the kidney, liver, and brain substance. In the 
skin, liver, heart, and lung, they are often secondary. 

7. Age. Sarcomas are most common between the ages of 
twenty and forty ; they may be congenital. 

8. Malignancy. They are malignant in two ways, (a) by recur- 
rence, and (b) by giving metastasis. Metastasis is most frequent in 
the skin, liver, lung, and heart. The pigmented forms are most 
malignant; next to these those composed of small round cells. 
Those growing rapidly are more malignant than those of slow 
growth. Peripheral sarcomas possess greater malignancy than 
those that are deep-seated ; this is particularly true of sarcoma of 
bone, and depends on the proximity of the tumor to the blood- 
vessels. Metastasis takes place through the blood-vessels. Occa- 
sionally there is a general deposit of sarcoma nodules all over the 
body — miliary sarcosis, or sarcomatosis. 



94 



NOTES ON PATHOLOGY. 



9. Etiology. Traumatism seems to play an important role in 
the pathogenesis of sarcomas, and the mechanical theory finds in 
them its greatest support. The sarcoma may develop immediately 
after an injury or from an old scar. 

VARIETIES OF SARCOMA. 



ROUND CELL SARCOMA. 

There are three forms of round cell sarcoma : (a) small round 
cell ; (&) large round cell, and (c) lympho-sarcoma. 

(a) Small Round Cell Sarcoma.— This is a rather soft, 
rapidly growing tumor which at times attains a larger size than 
any other form of sarcoma. On section it is somewhat translucent 
and pinkish-white, and on pressure several hours after removal 
exudes a milky fluid. In color it resembles brain substance or the 
flesh of fish. When large, the center may be cheesy ; hemorrhagic 
infiltration also occurs. 

Microscopy. The tumor consists almost entirely of small 
round cells with a large pale nucleus. There 
is only a very slight amount of intercellular 
substance, usually homogeneous, at times fib- 
rillar, around each cell. 

Stroma. A characteristic feature of cancer 

is the stroma which surrounds groups of epi- 

Smaii Round cdi Sarcoma, thelial cells. In sarcoma we do not find the 

connective tissue arranged in the form of chambers ; if it exists at 

all, it follows the course of the blood-vessels. 

Seats. The skeleton, intermuscular septa, subcutaneous con- 
nective tissue, skin, testicle, and ovary. 
In the last two it may be congenital. 
(b) Lympho - sarcoma. — The 

characteristic feature of this is the inter- 
cellular substance which resembles that 
found in lymphatic glands and consists 
of a delicate reticulum of branching 
cells. The meshes contain a few round 
cells which are smaller and stain more 

intensely than the cells of the small round cell sarcoma. 

The distinction from lymphatic gland is not always easy ; it is 

to be based on the mode of growth. The tumors are very 





Lympho-sarcoma. 



SPINDLE CELL SARCOMA. 95 

malignant ; they spring from lymphatic glands, and easily break 
through into the surrounding tissue; they also give metastasis and 
recur. 

(c) Large Round Cell Sarcoma.— This grows in the same 
localities and has the same appearance as the small round cell form, 
but is somewhat firmer. 

Microscopy. As a rule we find large irregular cells with a 
large amount of protoplasm and with nuclei of the same size as or 
larger than in the small round cells. Besides these there are other 
cells, small round and spindle cells and cells with several nuclei 
(polymorphous cells). The intercellular substance is small in 
amount. 

SPINDLE CELL SARCOMA. 

This is smaller and firmer than the round cell sarcoma ; the 
surface of section is fasciculated — like muscle — whence the name 
sarcoma (oapl, flesh) : its color, however, is not that of muscle, but 
pinkish and translucent. There is no milky fluid. The tumor is 
not veiy malignant ; the tendency to metastasis is small, but recur- 
rence is common. It is the latter property that caused surgeons to 
term it " recurrent fibroid." 

Microscopy. We find large numbers of spindle cells, which 
may be small or large in size ; they have 
an oval, vesicular nucleus, and run in 
bundles, which gives rise to the fascicu- 
lated appearance. The amount of inter- 
cellular substance is slight ; at times the 
presence of delicate fibrillar projecting 
from the ends of the cells contribute to 

the intercellular Substance. Large Spindle Cell Sarcoma. 

Sarcomas always possess some intercellular substance, a fea- 
ture which distinguishes them from carcinoma in which the cells are 
packed together without any such substance. 1 

Many spindle cell sarcomas are really polymorphous in char- 
acter. 

Seats. The skin, periosteum, bones, breast, intermuscular con- 
nective tissue, and testicle. It is the most common sarcoma. 




1 It is important to remember that intercellular substance and connective tissue are not 
synonymous terms. Intercellular substance refers to the material between the cells, and is possessed by 
all tissues, including connective tissue. 



NOTES ON PATHOLOGY. 



GIANT CELL SARCOMA. 

This is a sarcoma containing giant cells. The latter are large 
cells, with numerous pale vesicular nuclei generally grouped toward 

one pole of the cell. The protoplasm 
appears to have undergone a hyaline 
degeneration. As a rule the giant cells 
lie free in spaces, being separated from 
each other by intercellular substance, or 
by true connective tissue. The inter- 
cellular substance is a prominent feature 
in the giant cell sarcoma. 

The tumor does not generally consist 
solely of giant cells ; spindle cells and 
round cells are usually also present. It is comparatively benign. 

Seats. Bones, especially the jaws and about the knee-joint. 
The giant cell sarcoma of the jaw is commonly described as malig- 
nant epulis. Epulis is a tumor growing from the jaw ; it is fre- 
quently fibromatous. 




Giant Cell Sarcoma. 



ALVEOLAR SARCOMA. 

This tumor strongly resembles cancer from the fact that the 
sarcoma cells, usually of the round cell variety, are held in a 

stroma. This stroma is as a rule 
made up of spindle cells, while in 
carcinoma we find it composed of 
fully-formed fibrous tissue. At times 
the stroma is truly fibrous ; then the 
distinction from carcinoma becomes 
difficult, and has to be based on the 
character of the cells, which are of 
the connective tissue type in the one, 
of the epithelial in the other. 
The mode of development of alveolar sarcoma is obscure. 
Either previously existing bands of fibrous tissue fail to become 
sarcomatous, and remain, or the sarcomatous growth takes place 
along the adventitia of blood-vessels. Some forms cannot be ac- 
counted for on these theories. 

Seats. Moles of the skin, bone, serous membranes, especially 
that of the brain. 




Alveolar Sarcoma. 



PSAMMOMA. 97 

ENDOTHELIOMA. 

This is a sarcoma growing from the endothelial lining of lym- 
phatic spaces and blood-vessels. It forms diffuse, extensive masses 
on the surface of serous membranes. 

Microscopically, we find long branching cylinders of cells, the 
appearance being to a certain extent like that of alveolar sarcoma. 

Seats. Serous membranes — pleura, peritoneum, dura. 

MELANO-SARCOMA. 

This is a sarcoma containing melanin. The pigment granules 
are in the cells and intercellular substance ; the cell-nucleus is 
usually free from melanin ; nor are all the cells of the tumor pig- 
mented. Any of the types of sarcoma may become melanotic, but 
it is generally the spindle-cell form. 

Seats. They are found where pigment is normal — in the skin, 
the choroid coat of the eye, and the meninges. 

It is very malignant, especially when growing in the eye. Me- 
tastasis in that case is to the digestive tract, particularly the liver. 
Melano-sarcoma of the 'skin gives metastasis to the skin and the 
internal organs — the digestive tract, heart, and lungs. The second- 
ary deposits are generally, but not always, melanotic. 

CHLOROMA. 
This is a pigmented, round cell sarcoma growing from the 
periosteum of the skull. Its greenish color is due to a peculiar 
fatty degeneration. It is rather benign. 

PSAMMOMA. 
This is found in the ependyma of the brain, and is a sarcoma, 
really a fibro-sarcoma, in which the intercellular substance is infil- 
trated with lime. It is not very malignant. 



Other forms of sarcoma are the myxosarcoma, the lipo-sarcoma y 
or sarcoma lipomatodes, both of which occur in the subcutaneous 
connective tissue, the gliosarcoma, the chondrosarcoma, and the 
osteosarcoma. In the last two we have the sarcoma combined with 
cartilaginous and bony tissue, respectively. They grow from bone 
and from cartilage, although not all tumors of cartilage or of bone 
are chondrosarcoma or osteo-sarcoma ; they are also found in the 
parotid gland and testicle. The glio-sarcoma occurs in the retina,, 
rarely in the brain. 

7 



98 



NOTES ON PATHOLOGY. 



CYLINDROMA. 

This may be (a) a form of myxo-sarcoma, in which the 
myxomatous tissue is arranged in bundles or cylinders. (b) In 
some of the cylindromata the walls of the 
blood-vessels have undergone a hyaline 
degeneration, and are greatly thickened, par- 
ticularly in certain places. Subsequently the 
hyaline material becomes covered by a 
mantle of sarcoma cells, (c) The tumor may 
be produced by a myxomatous degeneration 
of an endothelioma. 




Cylindroma. 



SARCOMA IN THE LOWER ANIMALS. 
It is most common in the horse and 

dog, infrequent in cattle, very rare in cats. 
Gray horses are especially affected with sarcoma, the tumor being 
generally melanotic, growing from the pigmented tissues about the 
external genitalia and the anus. Two forms are met with : the hard, 
which is quite benign, and the soft, which is very malignant, and 
gives rise to general metastasis. Other sarcomas, when they occur, 
are the same as in man. 



ARCHIBLASTOMATA 



MYOMA. 



There are two forms, the rhabdomyoma, or striated muscle 
tumor, and the liomyoma, or non-striated muscle tumor. 

{a) Rhabdomyoma. — This is rare, and is most often con- 
genital, originating in the segmental organs of the fetus ; hence, we 
find it in after-life in the kidney, testicle, and, more rarely, in the 
ovary. Its occurrence in these localities is only explicable on 
Cohnheim's theory. It is usually combined with sarcoma, which 
endows it with the tendency to metastasis that it sometimes 
presents. 

A pure rhabdomyoma is found as a small tumor in the heart ; 
there is in this form no evidence of congenital origin. 

Microscopically , we find ordinary striated muscle fibers as well 
as striped spindle cells, the embryonal forerunners of the striped 
fibers. 



EPITHELIAL TUMORS. 



99 



(b) Liomyoma. — This is quite common, forming smaller or 
larger, well-circumscribed tumors, which on section show bundles 
of fibers running in different directions. 
Very often the tumor is combined with 
fibroma, myo-fibroma. 

Microscopy. Liomyoma is com- 
posed of long spindle cells with rod- 
shaped nuclei. It might be confounded 
with spindle cell sarcoma, but the rod- 
shaped nucleus is characteristic. 

Seats. The most frequent seat is 
the uterus (uterine fibroid). The tumor may be submucous, sub- 
peritoneal, or in the muscular wall itself — intramural. It is also 
found in the esophagus, the wall of intestines, and the prostate. 

Degenerations. Calcification ; myxomatous degeneration ; fatty 
degeneration ; softening with cyst formation ; cavernous change. 




Liomyoma. 



NEUROMA. 

A tumor containing nerve tissue. 

The neuroma proper should be distinguished from the false 
neuroma, which may be a fibroma, a myxoma, or a glioma. False 
neuroma growing along the nerves is often multiple. 

The true neuroma is of two kinds — the ganglionar and the 
fibrillar. 

(a) Ganglionar neuroma. This is rare ; it consists of ganglion 
cells ; fibers are also present. 

(b) Fibrillar neuroma grows along the course of nerves or in 
stumps, although in the latter locality it is often a false neuroma. 
The true fibrillar neuroma may be myelinic, or medullated, or 
amyelinic, or non-medullated. 

The multiple neuroma of the skin at times has a peculiar 
distribution — somewhat in the form of an intertwining network — 
it is then termed plexiform neuroma. 

EPITHELIAL TUMORS. 

The best designation for this class of tumors would be epithelio- 
mata, but as this word is habitually applied to certain forms of 
carcinoma, it cannot be used as a generic term. 

Although classed as epithelial growths, all the tumors contain 
connective tissue, for we can have no new growth consisting solely 



ioo NOTES ON PATHOLOGY. 

of epithelium. It is important in this connection to understand the 
relation of epithelium to connective tissue. Normally, the epithe- 
lium is on the surface, and beneath it is the connective tissue with 
the blood and lymphatic vessels. In certain places we find projec- 
tions of these tissues, in others depressions. The former are 
termed papilla, the latter glands. Epithelial tumors are simply 
exaggerations of these normal variations. 

In the simple epithelial tumors the histologic relation of epi- 
thelium to connective tissue is maintained, but the plan of structure 
is altered — the growths are atypical organoidally . These tumors 
are benign. 

There is another group, histologically atypical, in which the 
epithelium breaks through the connective tissue and forms separate 
nests directly in it ; these are the cancers. 

SIMPLE EPITHELIAL TUMORS. 

PAPILLOMA. 

It is frequently impossible, owing to a co-incident hyperplasia 
of the connective tissue, to separate epithelial from fibrous papillo- 
mata. Many papillomata are inflammatory, and are best classified 
as hypertrophies, being due to irritation. 

Examples are : (a) Callositas. This is a hyperplasia of the 
epiderm and the papillae. If it becomes excessive and projects both 
outward and inward, causing atrophy of the connective tissue 
papillae, it constitutes (J?) Clavus, or Com. 

Cornu CUtaneum, or Corn, is an enormous hypertrophy of 
the epiderm and the papillae that partakes of the character of a 
true tumor. A small blood-vessel generally penetrates into the 
horn. Horns are most frequent on the face and extremities ; they 
may become spiral. 

On mucous membranes we have also examples of papillary 
growths that are hypertrophies rather than tumors. They are 
common in chronic inflammation of the gastro-intestinal tract and 
the uterus, and are often dendritic in shape. 

True papillomatous tumors of mucous membranes may grow 
from squamous epithelium (hard papilloma), or from columnar 
epithelium (soft papilloma). The consistency depends also on the 
amount of connective tissue present. 



ADENOMA. 



IOI 



Papillomata may become cystic from myxomatous degeneration 
of the connective tissue; cysts may also arise from pressure on 
gland ducts. 

Seats. Larynx; nose; intestines, especially toward rectum; 
bladder. The papilloma of the uterus is usually an hypertrophy, 
and not a true tumor. 

Elephantiasis. — This is characterized by a hyperplasia of 
the skin and the subcutaneous connective tissue, and by dilatation 
of the lymphatic and blood-vessels. It is the result of repeated 
attacks of acute inflammation, erysipelatous in appearance, due as 
a rule to irritation of the lymphatic circulation {filaria sanguinis 
hominis). As evidence of the inflammatory nature of the affection, 
we find foci of round cell infiltration. 

In the circumscribed forms, those limited to the scrotum or 
labium, the cause, as already stated, is not evident, and it is proper 
to class them as tumors, leaving undecided the question whether 
they are fibromas, lymphangiomas, or simple epithelial tumors. 




ADENOMA. 

A normal gland may be compared to a properly constructed 
house. In such a house we have chambers (acini) and corridors 
(ducts) arranged after a definite plan, and 
composed of the masonry (connective 
tissue) and the plaster lining (epithelium). 
The plaster everywhere covers the walls. 
In an adenoma the relation of the plaster 
to the masonry (of the epithelium to the 
connective tissue) is normal, but the 
architecture of the house is faulty. In- 
stead of a proper proportion of chambers 
and halls, we have an excessive and purposeless multiplication of 
chambers (acini) without adequate halls, or a multiplication of halls 
(ducts) without corresponding chambers. An adenoma, therefore, 
is a gland- like tumor, histologically normal, but organoidally \ or 
architecturally, atypical. 

Continuing the comparison, and applying it to the cancers, we 
may say that in them the plaster no longer covers the walls every- 
where regularly, but that it breaks into the masonry and forms 
collections within the body of the walls. In other words, there is 
in cancers a histologic disturbance — they are histologically atypical. 



Adenoma. 



rot NOTES ON PATHOLOGY. 

* 
Varieties of adenoma. These are, histologically, (a) tubular, 

(b) racemose ; clinically, {a) circumscribed, (b) diffuse. 

(a) Circumscribed adenoma. This is a firm, well-circumscribed 
or encapsulated tumor, found in large glands — ovary, mamma, kid- 
ney, and liver ; it is benign, although that of the ovary may be- 
come malignant. 

(b) Diffuse adenoma. This develops on mucous membranes, 
forming flat swellings without definite outline. It is apt to become 
malignant. It is most frequent at the pylorus and in the body of 
the uterus. 

Pure adenomata are found in the breast and kidney, but are 
rare ; combinations are common. The latter are : 

(a) Cyst-adenoma. The cells continue to pour out their secre- 
tion, the pouches becoming thereby distended until they constitute 
cysts. This is the commonest form of adenoma, and is most 
frequent in the ovary (ovarian cyst). 

(b) Papillomatous adenoma, or adenoma papilliferum. In this 
we have a proliferation of the epithelium and connective tissue of 
the walls of the sacs into the interior of the acini in the form of 
arborescent growths. Seats. Ovary ; mamma. 

(c) Adeno-carcinoma. The epithelium breaks through the 
basement membrane and develops in the connective tissue. 

CARCINOMA. 

This is an epithelial tumor histologically atypical. 

The epithelial cells break through the basement membrane, 
and lie " naked " in the recesses of the connective tissue. 

The breaking through occurs usually in the form of solid plugs 
or cylinders, not in the form of glands. There is no intercellular 
substance between the cells (cf. sarcoma). 

The connective tissue which surround the cells is termed the 
stroma ; it is necessarily hyperplastic, and as evidences of its pro- 
liferation shows multiplication of cells (karyokinetic figures) and 
round cells in considerable numbers. Variations in the amount of 
connective tissue cause differences in the consistency of carcinomas. 
The stroma may be embryonal in character or dense ; or it may be 
the seat of degenerations. 

The epithelial cells frequently tend to reproduce the arrange- 
ment of the parent epithelium ; thus, in cancers of the mucous 



CARCINOMA. 103 

membranes, we find that there is an outer layer of cylindrical cells 
arranged in the form of a gland, the interior of the nest being filled 
with cells of a modified shape. 

Forms of cells. The cells have a tendency to resemble those 
from which they grow, (a) In skin cancers the cells are cuboidal 
like those of the rete mucosum ; they may undergo horny change 
and become flattened out ; they also tend to be arranged in whorls. 

(b) In cancer of mucous membranes, as the intestine, the epithelial 
cells are cylindrical and present a tendency to mucoid change. 

(c) In cancers of glands we find cells of glandular type; the 
degenerations are those of the parent epithelium — a fatty degenera- 
tion in cancer of the mammary gland ; sebaceous in that of the 
sebaceous glands. While, however, the cells in a certain degree 
resemble the epithelium from which they grow, they nevertheless 
show a marked irregularity in shape, due to mutual pressure. 
This gives rise to the polymorphous cells of cancer. 

The cells are large, irregular, have a pale, vesicular nucleus, 
and a large amount of protoplasm, the latter frequently presenting 
evidences of degeneration. 

Naked Eye Appearances. — (a) Primary cancers. These 
are rather hard ; they grow upon surfaces or in glands, forming in 
the latter large, deep-seated masses, pale, yellowish or reddish- 
white in color, not encapsulated, and extending by infiltration. 
On surfaces, particularly on mucous membranes, they are often 
papillomatous in character. Surface cancers are apt to ulcerate. 
Primary cancers as a rule are single. 

{b) Secondary cancers. These are sharply circumscribed, but 
not encapsulated ; they occur as multiple growths in the interior of 
organs, in the form of rounded, whitish masses. 

Degenerations. — These may affect the epithelium or the con- 
nective tissue. The epithelium undergoes the forms of degeneration 
peculiar to the parent cells : Fatty, in cases of cancer of the mamma ; 
horny, in that of the skin ; mucoid, in that of mucous membranes ; 
sebaceous, in that growing from the sebaceous glands. In these 
degenerations the cells maintain their individuality ; in other lorms 
large masses of cells are affected, either with fatty or cheesy change. 
Atrophy and absorption of the cells may be brought about by 
pressure of the stroma. Inflammation, the result of bacterial 
infection, leads to the formation of ulcers with thick, under- 
mined borders upon which papillomatous growths are frequently 



104 NOTES ON PATHOLOGY. 

developed. Calcification may occur, but is rare ; hemorrhage is 
more frequent from the tumor than into it. Cysts are common in 
carcinoma and result (a) from softening, (b) from retention of 
secretion, #hd (c) from proliferation of the epithelium. The last 
variety is produced by a hyperplasia of the epithelium of glands, 
which hyperplasia give rise, in the first place, to cysts and then, by 
penetration through the basement membrane into the connective 
tissue, to cancer — adeno-carcinoma. 

In the other varieties the cyst formation is a passive process. 
Cysts are common in cancers of the ovary and the mammary gland. 

Combinations. Carcinoma combines (a) with adenoma — adeno- 
carcinoma ; (b) in the parotid gland and testicle, with chondroma 
and myxoma, forming a variety of " mixed tumors." 

Seats. The seats of primary cancer, in the order of frequency, 
are: (i) vaginal portion of the uterus, (2) skin of face, (3) mamma 
of female, (4) pylorus, (5) rectum, (6) esophagus, (7) ovary, (8) 
testicle, (9) external genitals, (10) prostate and bladder, (11) 
pancreas, (12) kidney, (13) small intestines, (14) thyroid gland, (15) 
biliary passages, (16) liver, (17) bronchial tubes. 

Metastasis. Cancer extends (a) by gradual infiltration of the 
surrounding parts ; (b) by spreading along the lymphatic vessels, and 
ic) by dissemination through the blood-vessels, especially those ot 
the portal circulation. 

The seat of the secondary growths is at times peculiar, thus in 
general metastasis of cancer of the mammary gland, the bones are 
frequently involved. 

Seats of secondary cancer. (1) Lymphatic glands, (2) liver, (3) 
lung, (4) peritoneum and pleura, (5) spleen, (6) kidney, (7) brain, 
(8) skeleton. 

Course. The course of carcinoma is usually chronic, the dura- 
tion being a year or more. Pregnancy hastens the growth of mam- 
mary and uterine cancer; at times there is also a rapid spread 
along the blood-vessels, particularly in the abdominal cavity from 
cancer of the stomach or ovary. This is termed acute carcinosis, and 
is rapidly fatal. 

Effects. These are (a) those resulting from pressure, either 
upon gland ducts or upon other structures ; (b) the cancerous ca- 
chexia. The latter may be due (1) to hemorrhage, (2) to micro- 
organismal infection with consequent suppuration and septicemia, 
(3) to the production of a special cancer poison. 



SQUAMOUS CANCER. 



105 



Age. Cancers of the skin and of the intestines occur after 
forty ; uterine cancer at about thirty ; those of the kidney and the 
sexual organs early in life or even congenitally. 



VARIETIES OF CARCINOMA, 

Cancers are classified according to the character of the epithe- 
lial cells into {a) squamous, (b) cylindrical, and (c) glandular. 

SQUAMOUS CANCER. 

This is often termed epithelioma. It consists of flat or cuboi- 
dal cells, like those of the deeper layers of the skin. 

Seats. The skin, the 
muco-cutaneous junc- 
tions, and the mucous 
membranes covered with 
flat epithelium. Named 
individually, the seats 
are, the lips, nose, eye- 
lids, vagina, rectum, 
mouth, pharynx, glans 
penis, esophagus, cardia, 
bladder, and larynx. 

Macroscopy. The 
tumor begins in the form 
of a warty growth which 
infiltrates the surround- 
ing structures and pro- 
duces flat swellings that 

have a tendency, eSpeC- Squamous Epithelioma. 

ially on mucous membranes, to papillomatous formation. Ulcera- 
tion is common. The surface of section is whitish, and on pressure 
yields, from separate "points, an inspissated fluid consisting of epi- 
thelial cells and the juices of the tumor tissue. 

Microscopy. The epithelial cells are arranged in solid branch- 
ing plugs or masses, surrounded by the connective tissue stroma. 
The majority of cells, particularly those near the periphery of the 
nests, are cuboidal, like those of the deeper layers of the skin, 
but toward the center the cells are apt to be flat and to take on a 
peculiar concentric arrrangment producing whorls, termed pearly 




io6 NOTES ON PATHOLOGY. 

bodies. The cells tend to undergo a horny change; many also 
contain granules of eleidin and keratohyalin.* 

CYLINDRICAL CANCER. 

This is a cancer containing cylindrical epithelium. It is gen- 
erally termed cylindrical epithelioma. 

Seats. Mucous membranes covered by cylindrical epithelium, 
particularly the intestinal tract, from the cardia to the lower third 
of the rectum, and the uterus ; kidney, mammary gland. 

Macroscopy. It appears either as soft, whitish nodes, or as flat 
swellings, with a tendency to the formation of papillomatous 
growths. It is softer than the squamous cancer. 

Microscopy. Toward the periphery of the nests we find colum- 
nar cells, which are often converted into goblet cells by mucoid 
change. In the center of the nests the cells are altered by pressure* 

Cylindrical cancer is frequently combined with adenoma. 

GRANDULAR CANCER— CARCINOMA SIMPLEX. 

This is made up of polyhedral cells. 

Seats. Mamma, liver, salivary glands, pancreas, ovary, and 
testicle. 

Macroscopy. The tumor appears generally in the form of a 
node that is harder than the surrounding structures, although it is 
not usually a hard cancer. It may also occur as a diffuse infiltra- 
tion, particularly in the liver. 

Microscopy. The cells are polyhedral. 

CLINICAL VARIETIES. 
Cancers are classified clinically, according to their naked-eye 
appearance and consistency, into (a) hard, (b) soft and (c) colloid. 

Any of the types described above may 
assume any one of the clinical forms. 

{a) Hard, or Scirrhous Cancer, 
— The hardness depends on the amount of 
connective tissue ; the nests are small, the 
cells few. Here and there the alveoli are 
empty, from atrophy and degeneration of 
the cells. 

Seats. The mamma, where it is usually a glandular cancer ; 
the pylorus, where it may be glandular or cylindrical. 

* Many of the so-called parasites are simply granules of these substances. 





CHOLESTEATOMA. 107 

(b) Soft, Encephaloid, or Medullary Cancer.— This is a 

large, soft, juicy, whitish tumor, which, microscopically, shows very 
little connective tissue, but presents large 
nests containing many cells. Many cylin- 
drical cancers are encephaloid. 

Seats. Mucous membranes, testicle, and 
ovary. 

(c) Colloid Cancer, Carcinoma 
gelatinosum. — This is a carcinoma in which 
the epithelium has undergone a mucoid or a 
colloid change, most frequently the former. 

The tumor has an alveolar structure visible to the naked eye, the 
alveoli being filled with a gelatinous material producing a honeycomb 
appearance. 

Seats. Pylorus — here the degeneration is usually mucoid ; 
thyroid gland, and breast. 

Among rare forms of carcinoma we have the following : 

(a) Carcinoma myxomatodes.— One in which the stroma 
has undergone myxomatous degeneration. 

(b) Carcinomatous Cylindroma.— One in which portions 
of the stroma have undergone a hyaline change, the degenerated 
areas running in the form of cylinders through the tumor. 

(c) Giant-Cell Carcinoma.— In this the alveoli are rather 
small, and may contain one or two giant epithelial cells. The latter 
are termed physalids. There is considerable similarity between a 
giant-cell carcinoma and an alveolar large round cell sarcoma con- 
taining giant-cells. The differentiation depends on the general 
characters of sarcomas and carcinomas, and particularly on the fact 
that sarcoma cells may constitute the walls of blood-vessels — a 
thing epithelial cells never do. The stroma is as a rule abundant 
in giant-cell carcinoma. 

(d) Melano-Carcinoma. — One containing pigment — melanin. 

Cholesteatoma. — This is a benign epithelial tumor occur- 
ring in the central nervous system. It is distinct from carcinoma, 
and is best classified with the teratomata. Its existence in the brain 
is explained in concordance with Cohnheim's theory. It contains 
peculiar shining whorls, largely composed of cholesterin plates; 
sebaceous glands, hair, and other dermal structures may be 
present. 



108 NOTES ON PATHOLOGY. 

CARCINOMA IN THE LOWER ANIMALS. 

Cancer is rare in the lower animals, especially in herbivora ; it 
is more common in dogs and cats, occurring, in the first-named, in 
the breast, thyroid gland, prostrate body, and skin. In horses, 
when cancer develops, it is found in the skin about the penis or in 
the intestines. 

DIFFERENCES BETWEEN SARCOMA AND 
CARCINOMA. 

i. NAKED EYE APPEARANCE. 
Sarcoma. Carcinoma. 

Fleshy, smooth, rounded or bossellated. Nodular, with irregular outline, or an un- 

healthy ulcer, with papillary excrescences 
at borders ; base of ulcer indurated. 

2. SURFACE OF SECTION. 
Milky color, smooth, pearly, often with a More granular and opaque ; less apt to be 
reddish tint. reddish. 

3. JUICE. 
Absent as a rule. Present. 

4. ADIPOSE TISSUE. 
Absent. May be present. 

5. CAPSULE. 
May be present; if not, is pretty well cir- Very rare, 
cumscribed. 

6. RELATION TO SURROUNDING STRUCTURES. 
Usually not infiltrating locally ; may be seen Always infiltrating, 
with microscope. 

7. CONSISTENCY. 
Softer, with exceptions. Harder, with exceptions. 

8. RELATION TO SKIN. 
Not adherent ; if so, due to inflammation. Adherent. 





9. PAIN. 


Absent. 


Present. 




10. LYMPHATIC GLANDS. 


Not involved. 


Involved. 



11. METASTASIS. 
As a rule, along blood-vessels. Along lymphatics ; at times, along blood- 

vessels. 

12. RAPIDITY OF GROWTH. 
Varies, but may be more rapid than car- Growth rapid compared with other tumors, 
cinoma. except some sarcomata. 



ETIOLOGY OF CARCINOMA. fe 109 

13. AGE. 
Sarcoma. Carcinoma. 

Middle life ; not rare after ten years. After middle life. 

14. SITES. 

Connective tissue, e. g., corium, fasciae, Epithelial surfaces and glands — lips in male, 
intermuscular septa, bone, periosteum; vaginal portion of uterus in female; 

brain, ovary. Rare in liver, lung, uterus. breast, stomach, intestine. 

15. CELLS. 

Embryonal connective tissue cells, with Epithelial cells, packed without intercellu- 
slight intercellular substance. lar substance between partitions of con- 

nective tissue. 
16. STROMA. 
Slight intercellular substance between the Fully-formed fibrous tissue forming distinct 
cells, homogeneous or faintly fibrillar. alveoli. 

17. BLOOD-VESSELS. 
Embryonal, without distinct walls, simply Well-developed vessels in the stroma, 
channels with endothelial lining. 

ETIOLOGY OF CARCINOMA. 

During the last few years strong efforts have been made to 
discover the cause of cancer, but while these investigations have not 
been crowned with success, they have taught us two important 
facts : First, that cancer can be communicated from one individual 
to another ; secondly, that it can be inoculated from one animal into 
another. The majority of experimenters have looked upon protozoa 
as the cause of cancer, since they have found in the tumors certain 
bodies resembling gregarines and coccidia. If these bodies are 
really present, they are merely accidental and not causal ; in most 
instances, however, the bodies are not protozoa at all, but materials 
elaborated by the cancer cells. 

It should be stated that coccidia are at times found associated 
with hyperplasias of epithelial cells — thus in the biliary passages of 
the rabbit, coccidia are occasionally seen to produce papillary 
growths, with the cells arranged in layers. Similar bodies may be 
found in cancer ; also in Darter's disease, an affection of the 
sebaceous glands and hair follicles/ characterized by a hyperplasia 
of the epithelial structures. In molluscum contagiosum, in which 
there is likewise a hyperplasia of the hair follicles and sebaceous 
glands, the bodies are also present. 

In cancer the cyst-like bodies (coccidia) are found within the 
cells, pushing the protoplasm and nucleus to one side and growing 
until the entire cell is filled. Around the cyst is a capsule (whether 
formed by the parasite or by the protoplasm of the cell is not 



no NOTES ON PATHOLOGY. 

known). The coccidium divides into four sacs, each containing 
spores of future coccidia. 

Certain spindle-shaped bodies, with and without capsule, are 
also met with outside of the cells, but the greater part of the life- 
history of the protozoa is intracellular. 

While cyst-like bodies are quite common in cancer, spore- 
formations are rare, and when found, are an accidental and second- 
ary infection. 

In the majority of instances the cyst-like bodies have been 
demonstrated, by staining peculiarities and by chemical tests, to be 
substances elaborated by the cells — sometimes this substance is 
mucin, when in cancers the cells of which undergo this change ; 
in squamous epithelioma, the material is eleidin and keratohyalin. 

We are then forced to conclude that protozoa cannot be looked 
upon as the cause of cancer. 

CYSTS. 

There are two classes of cysts, those that are tumors and those 
that are not. The following are non-tumorous cysts : {a) Extravasa- 
tion cyst. This results from hemorrhage into the tissues, with 
subsequent absorption of the blood-pigment and encapsulation ot 
the fluid. 

(b) Softening cyst. This is due to circulatory disturbances, 
liquefaction necrosis, and encapsulation of the fluid. 

{c) Parasitic cyst. Of this the echinococcus, or hydatid cyst 
is an example. 

Cysts that are tumors, (a) Retention or Occlusion Cysts. 

— These are produced by the obstruction of gland ducts ; the secre- 
tion accumulates and distends the ducts. The cysts are lined by 
the epithelium of the gland. 

Varieties : i. Follicular cysts. These are small, cystic tumors, 
occurring chiefly in the skin, where they are due to occlusion of 
sebaceous glands {Comedo, atheroma). 

2. Mucoid cysts. These are commonly multiple, and originate 
from obstruction of the mucous glands of mucous membranes. 
They are found in the cervix uteri, mouth, lips, cheeks, antrum of 
Highmore {dropsy of the antrum), rectum, and larynx. 

3. Retention cysts of Large glands. These are found in con- 
nection with the salivary glands {ranuld), in the liver, and kidney. 
But not all cysts of the liver and kidney are retention cysts. 



CYSTS. hi 

4. Retention cysts of embryonal structures. These are congenital. 
They may occur in glands existing in later life, but the formation of 
the cyst was congenital. Examples are the parovarian cyst, a 
single congenital cyst of the parovarium ; certain cysts of the 
testicle and ovary ; hygroma of the neck, which may be either a 
congenital cyst or a lymphangioma ; cysts of the urachus and the 
suspensory ligament of the liver. 

(b) Teratoid, Teratomatous, or Dermoid Cysts.— These 
are of embryonal origin, but are not retention cysts. They are the 
results of errors in development, of misplacements of tissues which 
proliferate later in life and produce the structures that normally 
spring from them. Epithelium gives rise to epidermis, hair, teeth, 
etc. Teratoid tumors are usually cystic in character, a large portion 
of the contents being an atheromatous material like that found in 
sebaceous tumors. It consists of fatty matter, fat crystals, cholest- 
erin plates, fatty epithelial cells, hair, skin, sweat glands, sebaceous 
glands, teeth, etc. 

When very complicated, teratoid growths properly come under 
the head of monstrosities. 

(c) Proliferation Cysts.— These are really forms of 
adenoma {cyst- adenoma), which are produced by a proliferation of 
the epithelial cells of gland-acini, all the cells remaining attached 
to the basement membrane ; in consequence hollow spaces filled 
with the secretion of the cells are formed. Generally they are 
multiple new cysts being developed from the walls of larger cysts 
by a proliferation of the epithelium. 

Seats. — Ovary, most frequently, here constituting the ordinary 
multilocular cyst ; mammary gland, testicle, kidney, and liver. The 
majority of renal cysts are due to obstruction, but there are 
instances of proliferation cysts. 

Proliferation cysts show a marked tendency to the development 
of papillary growths into the interior of the spaces which may 
become entirely filled by sponge-like masses (cyst-ade7ioma papilli- 
ferum). Those of the mammary gland and ovary are especially 
apt to become papilleferous, a tendency that should excite suspicion, 
since these tumors are apt to become carcinomatous, solid epithelial 
masses being formed instead of hollow spaces. 

These cysts are lined by columnar epithelium, although they 
grow in organs, as mamma and ovary, which contain no such epi- 
thelium. This peculiarity is best explained in Cohnheim's theory. 



CHAPTER VII. 



SPECIAL PATHOLOGY. 

THE BLOOD. 

The blood is a fluid tissue which is the seat of active biologic 
changes, yet it is not directly under the control of the nervous sys- 
tem. The great mass of changes which it presents do not take 
place in it, but in the blood-forming and blood-destroying organs, 
which are under the influence of the central nervous system. 

The red corpuscles are formed in the spleen/bone-marrow, and 
lymphatic glands ; destruction of these corpuscles takes place, not 
in the blood itself, but in organs — the spleen and liver. The white 
corpuscles are formed chiefly in the lymphatic glands, also in the 
spleen. 

Usually, the blood contains 4,000,000] to 5,000,000 red cells, 
and 5000 to 10,000 white cells, per cubic millimeter, and hemo- 
globin to the amount of 14 per cent. 

I. Changes in the Total Quantity of the Blood.— (a) 

Plethora — an increase in quantity. (B) Oligemia — a decrease in the 
quantity. Both conditions are transient ; they result from excessive 
and deficient ingestion of food, respectively. In the case of olige- 
mia, other changes soon follow, usually a condition of hydremia 
develops. 

II. Changes in the Eed Corpuscles. — (a) Change in 
number. 

(a) Polycythemia — An increase in the number of red corpus- 
cles, a transitory condition usually due to the rapid removal of the 
watery constituents of the blood, as occurs in cholera. 

(/3) Oligocythemia — A decrease in the number of red corpuscles. 
This is a more frequent change, and is seen in all forms of anemia 
(using the term anemia in the general sense to denote an impover- 
ishment of the blood). 

Oligocythemia is said to be symptomatic y when the cause is 
apparent, and idiopathic, or essential, when no cause is discoverable. 

(112) 



THE BLOOD. 113 

Symptomatic oligocythemia is produced by (1) cachexia, (2) 
starvation, (3) wasting discharges, as in syphilis and tuberculosis, 
(4) poisons, as lead and arsenic, (5) infectious diseases, as malaria 
and syphilis, and (6) by hemorrhages. Essential oligocythemia is 
due to changes in the blood-forming and blood-destroying organs. 
Its causes are (1) leukemia, or leukocythemia, (2) chlorosis, and 
(3) progressive pernicious anemia. The last may at times be symp- 
tomatic. 

(b) Changes in size. The normal red corpuscle is 5-7/1 in diam- 
eter. In pathologic states we meet with (a) macrocytes or megalo- 
cytes, large corpuscles measuring 10-11^, and (j3) microcytes, small 
corpuscles, 2-4^ in diameter. Both forms indicate retrograde 
changes in the blood. 

(c) Changes in form. In anemia the red corpuscles are 
changed in outline, becoming irregular and misshapen. Such cor- 
puscles are called poikilocytes\ they are usually large and indicate 
destructive changes in the red cells. 

{d) In profound anemias the blood contains nucleated red cor- 
puscles. Their presence in the blood is ascribed to a rapid forma- 
tion of red cells, and their discharge into the blood-stream before 
they are sufficiently mature. They occur normally in the blood of 
the fetus. 

III. Changes in the Hemoglobin.— Normally, 14 parts 
of hemoglobin are found in 100 parts of blood. The clinical 
standard is entirely arbitrary. 

(a) Diminution — Oligochromcmia. This change depends upon 
one of two factors, (a) a dimunition in the number of red cells, 
each cell containing a normal, or even a greater amount of hemo- 
globin ; (/3) a decrease of the amount of hemoglobin in each indi- 
vidual cell. 

(b) Solution in the plasma — Hemoglobinemia. The causes of 
this are mineral poisons, such as potassium chlorate ; infectious 
diseases ; transfusion of foreign serum. If the hemoglobin passes 
out with the urine, the condition is called hemiglobinuria. 

(c) Changes in chemical composition. This is evidenced by a 
change in color, although not every change in color is indicative of 
a chemical alteration. 

The blood is (a) dark in asphyxia ; (j3) chocolate color in potas- 
sium chlorate poisoning ; (y) cherry-red in carbon monoxid poison- 
ing ; (5) dark or inky-black in sewer-gas poisoning. 



H4 NOTES ON PATHOLOGY. 

IV. Changes in the Leukocytes.— The average ratio of 
white to red cells is I : 700 ; it may vary normally from 1 : 1000 to 
1 : 500. 

An increase in the number of leukocytes is termed leukocy- 
tosis. Leukocytosis is physiologic (a) during digestion, and (b) in 
pregnancy. The pathologic conditions giving rise to it are (a) 
hemorrhage, (b) certain inflammations, (c) certain infectious diseases, 
(d) chronic diseases associated with anemia, the increase being abso- 
lute or relative (from diminution of the red corpuscles), (e) leukemia 
— in this disease there is an absolute increase exceeding that seen 
in any other condition, with a change in the proportion of the 
different forms. 

Fonus of leukocytes. Leukocytes are divided according to 
their size and the character of the nucleus into (a) small lympho- 
cytes, small cells with a large darkly-staining nucleus ; (b) large 
uninuclear cells with a feebly-staining nucleus ; (c) transitional forms 
— cells with an irregular, often sigmoid, nucleus, and (d) multi- 
nuclear leukocytes. The last are the most numerous in normal 
blood, constituting about 75 per-cent. of all white cells. 

The majority of leukocytes normally contain in their proto- 
plasm fine granules, which are neutrophile, i. e., when subjected, 
simultaneously, to an acid and a basic dye, they take a color midway 
between the two stains. The stains generally employed are eosin 
(acid) and methyl-blue (basic). Some of the cells contain granules 
of a larger size than the neutrophile cells — these granules take acid 
stains, and are termed eosinophile. Eosinophile cells have relatively 
small, though absolutely large, nuclei, which stain but feebly with 
the nuclear dyes. In the normal blood of adults, the eosinophile 
cells constitute from 1-2 per cent, of all leukocytes ; in the blood 
of children they are more numerous. While a proportion of 5 per- 
cent in an adult would point to serious disease of the blood-making 
organs, it would not do so in children. 

There is another form of leukocytes, rarely if ever present in 
normal blood, which contains large granules taking the basic stains, 
hence termed basophile. It is uninuclear, and corresponds to the 
mastzelle, granule cell, or wandering cell, found in the connective 
tissue. 

In physiologic leukocytosis the increase usually affects the 
neutrophile, multinuclear cells and sometimes the lymphocytes. 
In pathologic conditions, when the blood-making organs are 



THE BLOOD. 115 

diseased, the increase involves particularly the eosinophile cells. 
This is true especially of leukemia. It was maintained at one time 
that it was possible to determine, by the forms of leukocytes, which 
organs were affected in leukemia, but this cannot be done. 

In some cases of leukyocytosis, due to disturbances of the 
blood-making organs, the basophile cells are present in large num- 
bers — this is an indication of grave lesions of these organs. 

V. Changes in the Plasma.— -(#) Changes in the amount 
of water, (a) An increase — hydremia. This occurs in anemia, 
where it is relative ; in dropsy. (/3) A decrease — a?ihydremia. This 
is a transient condition, generally due to excessive watery dis- 
charges from the bowels, as in cholera. 

(b) Changes in quantity of fibrin factors, (a) An increase — 
hyperinosis. This exists when there is a tendency to thrombosis ; it 
is transient and not important. Sometimes it is rapidly produced 
by changes in the cellular elements of the blood. (/3) A decrease — 
hypinosis. 

(c) Particulate substances in the blood. A large variety may be 
found; sometimes they give rise to embolism. (1) Fibrin. (2) 
Pieces of heart valves. (3) Portions of tumors. (4) Particles of an 
atheromatous wall of a blood-vessel. (5) Gases. (6) Fat globules, 
in fractures of the long bones. (7) Pigment particles — usually 
hemosiderin, though frequently incorrectly termed melanin ; bile- 
pigment. (8) Charcot-Leyden crystals. These are octohedral 
crystals composed of phosphoric acid and a peculiar organic base ; 
they are never found in circulating blood, only in dead blood, espe- 
cially in leukemia. They are also met with in asthmatic sputum. 
There appears to be a connection between these crystals and eosino- 
phile cells ; both are found in the sputum of asthma as well as in 
leukemic blood. (9) Fat in the form of an emulsion, not in large 
droplets. An excess of fat in the blood (lipemid) occurs normally 
after the ingestion of large amounts of fat ; pathologically, we find 
it in diabetes. (10) Micro-organisms. In the majority of infectious 
diseases the micro-organisms do not develop in the blood ; there 
are, however, a few pathogenic bacteria that are essentially hemic, 
viz., the bacillus of anthrax and the spirillum of relapsing fever. 
The latter is found only in the blood and in the pulp of the spleen ; 
the former is found in the blood and in the tissues, at the site of the 
local lesions. Besides these staphylococci may at times be demon- 
strated in the blood ; also the influenza bacillus (this is doubted by 



u6 NOTES ON PATHOLOGY. 

some writers). Protozoa are also met with, as e. g., the plasmodium 
malariae. Protozoa are more frequent, however, in the lower animals. 
Finally, we have the embryos of the filaria sanguinis hominis. 

(d) Changes in chemical composition, (i) hicrease in the 
amount of albumin — hyperalbuminosis. This occurs in overfeeding 
and as a result of a loss of salts and water, as in cholera. (2) 
Decrease in the amount of albumin — hypalbummosis. Normally, we 
find from 70 to 80 parts of albumin per 1000 of blood ; in disease 
the proportion may sink to 50 per 1000. Hypalbummosis occurs 
in albuminuria, inanition, and anemia. (3) The presence of urates, 
especially of sodium urate — uratemia. This condition prevails 
during an attack of gout. We may at times have also an excess 
of uric acid in the blood. (4) An excess of urea — associated with 
uremia. The normal amount of urea in the blood is .16 parts per 
1000; in uremia it is from .4 to .6 per 1000. (5) An excess ot 
sugar — glycemia. In diabetes the amount may be doubled. (6) The 
presence of acetone — acetonemia — in diabetes. (7) The presence 
of toxins and antitoxins. 

Toxins are poisonous compounds elaborated by bacteria. Each 
bacterium produces its own specific toxin, regardless of the organ 
wherein it develops. Toxins, like drugs, have selective affinities for 
certain cells. The disturbances which they cause may be func- 
tional or structural, the latter being of a degenerative character. 
Toxins are eliminated by the excretory organs, especially by the 
kidney, and it is during their elimination that they determine the 
degenerative changes : first cloudy swelling, later fatty degeneration. 

Certain infectious diseases, it is well known, have a tendency 
to be limited, although the micro-organisms causing them are still 
present in the body. This limitation seems to be brought about 
by the presence within the blood of certain substances known as 
antitoxins. 

The toxins produced by the micro-organisms, which are, as 
has been said, specific, are carried in the circulation and exert a 
peculiar stimulating influence upon the body cells, on account of 
which the latter elaborate a specific antitoxin, which counteracts 
the toxin. An animal charged with a large amount of antitoxin is 
immune to the corresponding disease. That the immunity is due to 
a substance circulating in the blood is proved by the fact that 
when the blood-serum of this animal is introduced into another 
animal, the latter becomes also immune. The immunity of the 



THE BLOOD. 117 

first animal is termed active, since the antitoxin was produced by- 
its own cells ; that of the second is called passive, and is much less 
lasting. 

The living blood has a destructive action on micro-organisms, 
but this germicidal action is to be distinguished from the influence 
of antitoxins in the production of immunity. The latter is a specific 
property acquired by the blood in consequence of the introduction 
of certain toxic substances. 

A state of immunity may be produced against poisons that are 
not bacterial in origin. Ehrlich experimented with ricin, an albu- 
minous substance found in the castor-oil plant, and with abrin, the 
active principle of abrus, or jequirity seed. Both are irritant 
poisons, but when animals are fed with small doses, they are made 
immune against toxic quantities of these substances. This immu- 
nity is not a toleration, such as we see after the prolonged use of 
arsenic or morphin, for it comes on suddenly, and at a definite time 
— in about fifteen days. Ehrlich also proved that the blood of the 
immune animal contained an antitoxin, and that the latter was a 
direct chemical antidote to the toxin. He did this by mixing a little 
of the blood-serum of the immune animal with the poison in a test 
tube, and finding that the mixture was harmless when introduced 
into unprotected animals. 

In producing immunity against diphtheria, the toxin is first 
separated from the bacteria by filtration, and then is gradually in- 
troduced, in ascending doses, into horses until these no longer re- 
act to large amounts. The animals are then immune, and their 
blood-serum can be employed to confer immunity upon other 
animals. 

In diphtheria, and also in tetanus, the laboratory experiments 
upon animals have yielded perfectly satisfactory results ; in the case 
of the human subject the success has not been so positive. 

We find in the normal metabolism of the body instances com- 
parable to the reaction of the cells in infectious diseases : the liver, 
for example, counteracts the poisons produced during digestion. It 
is also known that the gastric cells, which normally elaborate an 
acid juice, secrete an alkaline fluid when acids are given ; while the 
salivary glands, the secretion of which is naturally alkaline, under 
the influence of acids secrete an excess of alkaline fluid. 

In regard to the mode of action, and the source of the anti- 
toxins, the theory of Ehrlich — that the body cells elaborate a chemical 



H8 NOTES ON PATHOLOGY. 

antidote — seems to be the best (Professor Guiteras). There are 
however, some weak points in this theory, for it is not always possi- 
ble to demonstrate a chemical antidotal action. It has, therefore, 
been asserted by some authorities, that the action of the antitoxins 
is not a chemical one, but that they, the antitoxins, protect the body 
cells, i. e. } render them immune against the toxin, instead of neu- 
tralizing the latter. This theory, evidently, is not an explanation at 
all. 

As to the origin of the antitoxins, it is claimed that they may 
be produced by the bacteria themselves. Strong arguments can be 
brought forward in favor of this view, but it seems doubtful whether 
we shall ever be able to settle the question conclusively. Whatever 
view we may take, we must accord to the body cells an important 
function, be it that they produce the antitoxin, or that they supply 
a favorable nutriment for its production. 

Not all the cells of the body are equally concerned in the 
formation of the antitoxin, but especially those that are directly 
acted upon by the toxins, usually those nearest the point of inocu- 
lation. This statement is based on the fact that immunity can be 
induced against certain diseases only in certain directions. Pasteur 
discovered a vaccine against splenic fever. When this vaccine is 
inoculated beneath the skin, the animal is immune to anthrax intro- 
duced in the same way, but the immunity is much weaker or absent 
when the poison is introduced through another channel, as the in- 
testine or lung. 

These facts seem to show that the cells first acted upon by 
the toxin react with the formation of an antitoxin — perhaps it is the 
cells of the lymphatic glands. 

The subject of antitoxins and immunity seems destined to 
revolutionize medicine. It is quite possible that the agents which 
are held of great account in the treatment of infectious diseases, 
derive their value from their power to stimulate the production of 
antitoxins. From this point of view our drugs and remedial meas- 
ures should be examined. 

Diseases of the blood, (a) Simple anemia, (b) pernicious anemia. 

The second may be considered an aggravated form of the 
simple anemia. We find in both the same changes, in kind, in the 
blood, but they are more marked in the pernicious anemia. In 
addition, the latter is associated with disturbances in the blood- 
making and blood-destroying organs — the spleen, lymphatic glands, 



THE BLOOD. 119* 

liver, and bone-marrow. The last becomes red and " splenified ;" 
the liver is the seat of an excessive pigmentary deposit. The 
marrow changes may indicate a rapid formation of red corpuscles, but 
also an active destruction ; the pigmentation of the liver certainly 
points to destruction of the red cells. 

Blood-changes in simple and in progressive pernicious anemia. 
(1) Oligocythemia. (2) Proportionate oligochromemia. (3) Hydre- 
mia. (4) Diminution of the specific gravity. (5) Diminution of the 
alkalinity. (6) Microcytosis. (7) Macrocytosis. (8) Poikilocytosis, 
especially marked in the pernicious form of anemia. (9) Presence 
of nucleated red corpuscles. (10) Relative or slight absolute leuko- 
cytosis. (11) Fatty degeneration of the parenchyma of organs, 
especially of the heart, kidney, and liver, of the blood-vessels, the 
nerve-structures and retina. 

Many cases of progressive pernicious anemia are not essential, 
but symptomatic, as, e. g. y those due (1) to intestinal parasites, as 
the anchylostomum ditodcnalc (constant abstraction of blood) ; the 
bothriocephalic latus ; (2) to cancer; (3) to grave disturbances of 
digestion, the primary cause of which, in a certain group of cases, 
is atrophy of the mucous membrane of the stomach. 

(c) Chlorosis. The characteristic features of this essential 
anemia are as follows: (1) Disproportionate oligochromemia. (2) 
Oligocythemia, of less degree than in ordinary anemia. (3) Di- 
minished specific gravity. (4) Hydremia. (5) Increased alkalinity. 
(6) Only slight changes in the form of the red corpuscles. In a few 
cases there is (7) hypoplasia of the sexual organs in females, and (8) 
hypoplasia of the heart and large blood-vessels. The last cannot 
be considered, as has been done by some, as the cause of chlorosis, 
but it is likely that cases presenting that condition are more liable 
to terminate fatally. Death in chlorosis is usually due to profound 
nervous disturbances — hysteria and hystero-epilepsy. 

(d) Leukemia. The features of this anemia are : (1) Oligo- 
cythemia. (2) Proportionate oligochromemia. (3) Extraordinary 
leukocytosis, affecting especially the multinuclear eosinophiles, and 
causing, in some cases, the appearance of a new variety — the 
basophiles. (4) The changes in the blood-making organs are 
marked — there is hyperplasia of the lymphadenoid tissue of the 
lymph-glands, the spleen, and the bone-marrow, either of each alone 
or of all. The lymphoid tissue may become hyperplastic through- 
out the body. (5) The shed blood contains Charcot-Leyden crystals. 



120 NOTES ON PATHOLOGY. 

(e) Melanemia. In this the hemoglobin becomes precipitated 
as fine granules in the blood-plasma, the red cells, or the leuko- 
cytes. The granules have been termed melanin — an unfortunate 
name, since melanin is really a metabolic pigment. Melanemia 
occurs in malaria. 

(/") Hcmoglobinemia. This is a condition in which the hemo- 
globin is in solution in the plasma. Its causes are mineral poisons, 
certain infectious diseases, and the transfusion of blood from another 
species of animal. 



CHAPTER VIII 



DISEASES OF THE LYMPHATIC GLANDS, 

THYMUS GLAND, BONE-MARROW, 

AND SPLEEN. 

AnatOHly . — A lymphatic gland consists of a large number ot 
nodes of lymphadenoid tissue within a fibrous capsule, that sends 
numerous trabecular into the gland. The nodes, which are spheri- 
cal in the cortical and pyramidal in the medullary portion of the 
gland, are made up of a reticulum of stellate cells, the meshes ot 
which are filled with lymphocytes. To the stellate cells endothelial 
cells are attached ; endothelial cells also cover the trabecular. In 
some places the lymphoid tissue is packed densely against the 
trabecular; in others there are spaces known as the lymphatic 
sinuses, between the lymphoid tissue and the trabecular. 

Functions. — I. Lymphatic glands form leukocytes; probably 
all leukocytes are formed in lymphoid tissue. 

2. They may form red corpuscles or certain leukocytes which 
change into these. 

3. They act as» filters, arresting especially micro-organisms intro- 
duced from without. 

Inflammation. Lymphadenitis. — The gland is enlarged, 
red, juicy, and surrounded by an inflammatory edema. The red- 
ness is most marked in the cortex ; minute hemorrhages may be 
present. On microscopic examination we find large numbers of 



LYMPHATIC GLANDS 121 

round cells ; the lymph sinuses are packed with lymphocytes, and 
epithelioidal cells derived from the endothelium. In addition, ( we 
find cells from the original focus, i. e., the lymphatic radicles ; also, 
micro-organisms. 

Cause. The inflammation is always secondary to a similar 
process in the radicles of the gland. 

Terminatio7is. (a) Resolution, the most frequent termination. 
The gland, at first red, becomes pale from pressure on the blood- 
vessels ; later, when resolution is in progress, it again turns red or 
" splenified," from secondary congestion after the removal of the 
inflammatory exudate. 

(b) Suppuration. This manifests itself very early to the eye as 
minute yellow spots. Under the microscope we find a large accum- 
ulation of multinuclear cells, with a tendency to breaking down. 
Parts or the whole of the gland may suppurate ; the process may 
even extend to the capsule and to the surrounding tissues, as, e.g., in 
chancroidal buboes. The abscess discharges and leaves a fistulous 
tract, healing by granulation. 

(c) Fibroid change. This depends upon a hyperplasia of the 
connective tissue of the trabeculae, with fibrous change. 

(d) Cheesy necrosis. This is most frequently due to tubercu- 
losis. The gland may be affected as a whole or in part ; it loses its 
translucency and elasticity, and becomes white and cheesy. Micro- 
scopically, the process is characterized by a marked proliferation ot 
the endothelial cells of the lymphatic spaces — a desquamative 
catarrh, we might say, of the lining of these spaces, comparable to 
caseous pneumonia. Miliary tubercles may be present ; at times 
they constitute the sole lesion of tuberculosis. Tubercle bacilli are 
generally found only in small numbers, if at all, but the tuberculous 
nature of the inflammation can be proved by inoculation into ani- 
mals and by the reaction which the patients give after the injection 
•of tuberculin. 

The glands may become calcified, or they may break down 
and discharge through long sinuses ; or fibroid changes may take 
place. 

Chronic inflammation of the lymphatic glands has been called 
scrofula; in the majority of instances scrofulous glands are tuber- 
culous. 

It is generally possible to demonstrate disease of the radicles 
of the lymphatic glands ; at times no peripheral lesion is found. 



122 NOTES ON PATHOLOGY. 

Causes of inflammation of lymphatic glands. I . Septic infection. 
The changes are the same as those in the radicles of the glands, 
usually suppurative. Example : the chancroidal bubo, which is 
probably due to virulent forms of pyogenic organisms. 

2. Glanders. The glands are involved more often in the lower 
animals than in man. Suppuration is common ; there is nothing 
specific save the bacillus of glanders. 

3. Anthrax. The glands are the seat of a permanent conges- 
tion, and are " splenified." Large numbers of anthrax bacilli are 
present. 

4. Typhoid fever. Characteristic of this disease is the hyper- 
plasia of the lymphoid tissue, particularly of the intestines, mesen- 
teric glands, spleen, etc. The bacillus is present. In the glands 
there is at first a transient congestion, soon succeeded by a marked 
anemia due to the proliferation and dense packing of the cells. 
The anemia leads to softening, which, however, is not a true sup- 
puration. The softening gives rise to ulceration in the intestines. 
In the glands necrosis is rare ; it may occur and cause rupture into 
the peritoneal cavity, peritonitis following, or into a vein, with the 
production of embolism. 

5. Syphilis. This affects all the glands of the body. There is 
a chronic hyperplasia, with a tendency to fibroid change ; the blood- 
vessels and trabecular are thickened. Gummy tumors may also 
occur. At times syphilitic glands present nothing differing from 
the hyperplasia due to other causes. 

6. Tuberculosis. 

7. Leukemia. In lymphatic leukemia the glands are greatly 
enlarged. 

8. Pseudo-latkemia, or malignant lymphadenoma. The appear- 
ance is the same as in leukemia, but it is said that the lymph spaces 
of leukemic glands can be more readily injected than those of 
pseudo-leukemic glands. It is really proper to speak of two kinds 
of malignant lymphadenoma — a leukemic and a non-leukemic. The 
non-leukemic lymphadenoma partakes of the character of a tumor ;. 
the leukemic seems to be of an infectious nature. But there is as 
yet no pathologic evidence for either of these views ; the statements 
rest upon clinical observations. 

9. Leprosy. The bacillus is present. 

10. Plague. This gives rise to acute suppurating buboes. 



THE SPLEEN. 123: 

The glandular enlargements, if chronic, are often called lymph- 
omas ; and we speak of hard and soft lymphoma, according to the 
amount of connective tissue present. 

Tumors. Lympho-sarcoma ; endothelioma ; other sarcomas 
may be primary (rare) or secondary ; secondary carcinoma. 

THE THYMUS GLAND. 

In structure and function the thymus resembles a lymphatic 
gland. It is divided into lobules by trabeculae, which are lined by 
endothelial cells ; between the trabeculae we find lymphoid tissue. 
As an evidence of its epithelial origin, we have the presence of con- 
centric bodies of flat cells {corpuscles of Hassall). 

Weight. At birth the thymus weighs 13 grams; at the end 
of the first year, 19 grams ; at the end of the second, 26 grams. It 
remains stationary until fourteen, then begins to atrophy, disappear- 
ing entirely by the twentieth year. 

Fatty degeneration. This is physiologic. 

Calcareous infiltration may occur. 

Circulatory disturbances. Parenchymatous hemorrhage is met 
with in asphyxia in the young ; in purpura. 

Inflammation. This is generally suppurative, being either of 
hemic origin or resulting from extension. 

Tumors. Lymphadenoma, i. e. y hyperplasia of the lymphoid 
tissue, is met with in leukemia and pseudo-leukemia in children. 

The enlargements of the thymus may give rise to asphyctic 
symptoms from pressure on the trachea. 

Tuberculosis and syphilis may attack the thymus gland. 

THE SPLEEN. 
The spleen is surrounded by a fibro-elastic capsule, from which 
trabeculae extend into the organ, dividing it into spaces in which 
we find the peculiar elements of the spleen, the Malpighian bod- 
ies, and the splenic pulp. The Malpighian bodies are lymphoid 
nodules surrounding the walls of the arteries. They are numerous, 
generally rounded, in places elongated ; their structure is identical 
with that of lymphatic glands. In the pulp the blood-vessels cease 
to have distinct walls, and break up, the endothelial cells lying 
loosely together without any definite arrangement. The pulp, there- 
fore, is composed of the endothelial cells of the flayed-out blood- 
vessels. 



I 34 NOTES ON PATHOLOGY. 

Functions, (a) The formation of red corpuscles, as evidence of 
which we have the existence in the spleen of nucleated red cells 
and the presence of red corpuscles in the protoplasm of some of the 
splenic cells, (b) The destruction of red corpuscles is rendered 
probable from the presence of pigment granules in the cells, (c) 
The neutralization of toxins, (d) The destruction of micro-organ- 
isms has been considered one of the functions of the spleen. It is 
highly probable that the spleen has no such action. 

Size and weight. The spleen is 14 cm. long, 9 cm. wide, and 
3 cm. thick, and weighs 200 grams, the ratio to the body weight 
being 1:400 (.25 per cent.). 

MORBID PROCESSES. 

1. Fatty Degeneration.— This occurs in the spleen, but 
possesses no clinical importance. 

2. Amyloid Degeneration.— Two forms of this degenera- 
tion are described : the circumscribed [sago-spleen) and the diffuse. 
The former affects the Malpighian bodies, which appear as semi- 
opaque, grayish nodules on the dark background of the spleen. In 
the diffuse we have a uniform degeneration of the organ. 

Amyloid disease is generally connected with cachectic condi- 
tions depending upon chronic suppuration. 

3. Pigmentation. — This is quite common, and is most 
marked in malaria, in which the spleen is of a slate color. The 
pigment is in the pulp and the trabeculae. 

4. Atrophy. — This may be produced by symptomatic anemias 
and by starvation. 

5. Circulatory Disturbances.— (a) Hemorrhagic or anemic 
infarction , the result of embolism, both infarcts occurring with 
about equal frequency. By their healing, deep scars are produced. 
If the emboli are specific, the effect will be abscess formation, either 
a single large, or many small abscesses. 

ili) Passive co?igestion gives rise to cyanotic indication of the 
spleen, in which we find thickening of the capsule and prominence 
of the trabeculae, the organ being firmer and also darker. The cause 
is generally cirrhosis of the liver or valvular heart disease. 

6. Composite Morbid Processes.— It is impossible, on 
account of the absence of the blood-vessel walls, to distinguish 
between active hyperemia and true inflammation, or between either 
of these and the acute enlargements in infectious fevers. 



THE SPLEEN. 125 

I. In infectious diseases the enlargement may be very great ; it 
is sometimes spoken of as acute splenic tumor. 

Among the most common causes are malaria and typhoid fever. 
The spleen is enlarged and darker ; the capsule is thinned from 
stretching, although in malaria, from frequently repeated swellings, 
the capsule may become thickened ; the organ feels harder, but when 
cut open is really much softer, and, on section, has a peculiar gran- 
ular appearance from the protrusion of the pulp. The projecting 
granules can easily be scraped off with the knife ; a considerable 
amount of blood oozes from the surface of section. Under the 
microscope we find a hyperplasia of all the elements, the lymphoid 
structure and the splenic tissue proper. There is an increase in the 
number of lymphocytes, free nuclei, and cells containing red 
corpuscles, and of the pigment. 

In certain infectious diseases, as in scarlet fever and in some 
cases of typhoid fever, the hyperplasia affects particularly the lym- 
phoid bodies which stand out prominently on section, resembling 
miliary tubercles. They may be distinguished from the latter by 
the fact that they are cut through when the section is made, are 
often irregular in shape, and do not contain the bacillus. 

In the acute splenic tumor we may find the micro-organisms 
of the particular infectious disease, often when they cannot be found 
elsewhere. This is especially true of anthrax, malaria, and typhoid 
fever. The micro-organisms may be obtained by tapping the spleen. 

II. Suppuration of the spleen is the result either of the 
extension of the suppurative process from neighboring organs or of 
septic embolism. 

III. Chronic Indurative Splenitis.— This is most fre- 
quently of malarial origin, being the result of repeated acute attacks 
of the disease. It is termed " ague-cake." There is, histologically,, 
a marked hyperplasia of all the elements of the spleen, with a 
tendency to the formation of fibrous tissue, particularly in the 
trabecular. The color is very dark, from the presence of an 
excess of pigment. In some instances the hyperplasia affects es- 
pecially the tissues of the capsule and trabecular ; the spleen is then 
hard, irregular on the surface, and adherent to surrounding struc- 
tures. The organ may return to normal. The condition of fibroid 
spleen is comparable to cirrhosis of the liver, and is a later stage of 
the uniform enlargement. The size, therefore, though still greater 
than normal, is less than it was primarily. 



126 NOTES ON PATHOLOGY. 

In the leukemic spleen the enlargement may be of the same 
nature as in malaria, i. e., a hyperplasia of all the elements. At 
times, however, the lymphoid follicles are especially affected, and, 
becoming prominent, give to the spleen a marbled appearance. 

In the uniform leukemic enlargement the spleen has a cherry- 
wood color ; the differentiation from malaria is difficult — it depends 
upon the presence, in the case of the latter, of pigment and the 
parasite. 

Hodgkiris disease {splenic anemia) may be associated with 
splenic enlargements, like those of leukemia. It is at present diffi- 
cult to say whether the changes in leukemia and Hodgkin's disease 
are primary or secondary. 

Tuberculosis. — This is not rare in the spleen, and is usually 
secondary ; although occasionally the spleen is the only part 
affected. There are two forms — (a) miliary tuberculosis, and (b) 
caseous tuberculosis. Both, as a rule, are the result of hemic 
infection, rarely of extension. 

Syphilis, — Gummy tumors are rare, as they are in all viscera 
at the present time. They are multiple, translucent, yellow, encap- 
sulated nodules, and have radiating from them bands of fibrous 
tissue. The spleen itself is fibroid, and the capsule thickened. 

Tumors. — I. Leukemic and pseudo-leukemic enlargements are 
sometimes classed as tumors — lymphadenoma. 2. Sarcoma, gene- 
rally secondary melanotic sarcoma. 3. Cancer is always secondary; 
the so-called primary cancers are endotheliomata. 4. Endotheli- 
oma. 5. Cavernous Angioma. 6. Lymphatic cysts. 

Malformations. — The organ maybe absent without the health 
being impaired. When removed from animals and man, other lym- 
phoid tissues, as the bone marrow, become hyperplastic and spleni- 
fied. Supernumerary spleens are frequent ; they may hypertrophy. 

THE MEDULLA OF BONE. 

The medulla of bone is comparable to a lymphatic gland. It 
consists of a connective tissue reticulum holding in its meshes lym- 
phoid cells, large cells with large nuclei, and giant cells. Some of 
the large cells contain red corpuscles ; they are especially abundant 
in acute anemias. Free red corpuscles, with and without nuclei, 
are also present. 

In early life the marrow is red ; in the long bones of the adult 
it is fatty and useless as a blood-forming organ, but in certain 



THE PERICARDIUM. 127 

forms of anemia, especially in acute and in pernicious anemia, there 
is a tendency for it to return to the red or embryonal condition. 

Suppuratio?i. In general septic infection the medulla of bone 
may be involved ; suppuration may also begin in the marrow and 
extend outward. 

Changes in the marrow in anemia. In pernicious anemia the 
marrow often becomes soft and splenified. In leukemia {myelogenic 
forni) we may have a uniform hyperplasia, as in the case of per- 
nicious anemia, or a proliferation of the lymphoid elements alone ; 
in the latter case the marrow has a marbled appearance. 



CHAPTER IX. 



DISEASES OF THE CIRCULATORY ORGANS. 

THE PERICARDIUM. 

The pericardium is a shining, transparent, serous membrane, 
forming a closed sac, which normally contains from 30 to 100 c. c. 
of clear fluid. 

Infiltrations and Degenerations.— i. Fatty infiltration. 
This occurs in advancing life, in general obesity, and in certain 
anemias. It affects chiefly the visceral layer, but may extend into 
the substance of the heart, into the connective tissue between the 
muscle fibers. The pressure of the fat causes the muscle fibers to 
atrophy and to degenerate. 

2. Calcification. Plates of lime are deposited in fibrous patches, 
the result of previous inflammation. These patches may undergo 
fatty degeneration before becoming calcified. 

3. Serous or dropsical infiltration occurs in conditions of general 
dropsy. The sac may contain an enormous quantity of fluid, which 
embarrasses the heart by pressure. 

4. Myxomatous degeneration. This generally involves the 
visceral layer, giving to it a swollen, jelly-like appearance. 

Circulatory Disturbances.— i. Hyperemia. This occurs 
in inflammations; if intense, it may lead to small hemorrhages. 



128 NOTES ON PATHOLOGY. 

2. Hemorrhage. The causes of hemorrhage are — (a) inflam- 
mation, (b) the purpuric diseases, (c) infectious diseases, especially 
septicemia, (d) asphyxia, (e) certain forms of poisoning, as by phos- 
phorus. In all of these conditions blood is generally present in the 
membrane, and also tinges the fluid. 

Large quantities of blood may be poured into the sac (liemo- 
pericardiiun) in cases of rupture of an aortic aneurysm, and rupture 
or wound of the heart itself. Death is usually instantaneous ; if 
not, the blood speedily coagulates. 

Inflammations. — Four varieties are described : (a) serous, 
(b) fibrinous, (c) sero fibrinous, and (d) purulent. 

(a) In serous pericarditis the sac is filled with a large amount 
of clear fluid containing only a few flocculi of fibrin, which are easily 
overlooked. Some fibrin may usually be found on the pericardium, 
in the grooves between the vessels. 

(5) In fibrinous pericarditis the quantity of fluid is small, but 
there is a great deal of fibrin ; adhesions between the pericardial layers 
are apt to form. The constant friction between the two surfaces of the 
membrane causes the fibrin to assume peculiar forms ; it may be 
disposed in ridges or lumps, or in the shape of small, villous-like 
projections (cor villosuni). The fibrin is quite firm, and gives to the 
hand the sensation of the cat's tongue. 

The membrane itself is opaque, and dotted over with minute 
hemorrhages ; the fluid is turbid, blood-stained, and contains small 
flocculi. 

The serofibrinous pericarditis is a combination of the two forms 
just described. 

Microscopy. In the microscopic section we note the deposit of 
fibrin, a breaking-down as well as a proliferation of the endothelial 
cells, the presence of leukocytes within the fibrin, and a round-cell 
infiltration with multiplication of the connective tissue cells in the 
deeper layers. New blood-vessels are also seen ; it is their rupture 
that is responsible for the small hemorrhages observed in the mem- 
brane. The elastic tissue generally marks the point of separation 
of the new tissue from the normal part of the pericardium. 

Terminations. i. Absorption. 2. The formation of fibrous 
patches, especially. in the visceral layer (milk spots). 3. Partial or 
complete adhesion of the two layers. 4. Calcification. 

Milk spots are localized patches of thickening, variable in size, 
whitish in color, and most frequent in the epicardium. They are 



THE HEART. 129 

either the result of a simple fatty degeneration or of a previous 
inflammation, the remains of a localized pericarditis. 

Effects of pericarditis on the heart. 1. Mechanical effects, from 
the pressure of the fluid. 2. Extension of the inflammation to the 
connective tissue of the heart itself, producing an interstitial myo- 
carditis. 3. The pressure of adhesions and the obstruction offered 
by them to the heart's action lead primarily to hypertrophy of the 
heart ; later, from interference with the nutrition of the organ, to 
atrophy. 

In purulent pericarditis the pericardium is covered with a 
creamy layer of pus and fibrin. The cavity contains a thick 
exudate consisting also of pus and fibrin. The micro-organisms 
reach the heart either through the circulation or by extension from 
neighboring organs. 

Etiology*. — Rheumatism, Bright's disease, and infectious fevers 
are the most frequent causes of pericarditis. Of the last, septicemia 
and pyemia produce a purulent inflammation ; pneumonia usually 
the sero-fibrinous, occasionally the purulent pericarditis. 

Tuberculosis is the result of hemic infection, and is then miliary, 
or of direct extension from adjacent structures, when it is either 
miliary or in the form of a diffuse cheesy mass. The tubercles are 
always best seen toward the base near the root of the large blood- 
vessels. 

Tumors are rare, and practically never primary. The most 
frequent is the secondary sarcoma, as a rule melanotic. Other 
tumors are the result of extension of new growths from neighbor- 
ing organs. 

THE HEART. 

The weight of the heart at different periods of life is as follows r 

At birth = 21 grams. 16-20 years = 218-234 grams. 

1 year = 37 " 20-30 " = 260-294 " 

2-5 years = 50-70 " 30-50 " = 297-308 " 

6-10 " = 77-"5 " 50-65 " = 318-332 « 

H-15 " = 130-205 " 

After 65, the weight diminishes to 300 grams. 

Proportion to body weight 1:175 

Length of left ventricle 8-9 cm. 

Thickness of left ventricle 7-10 mm. 

Thickness of right ventricle 2.5-4 mm. 



13° NOTES ON PATHOLOGY. 

The heart consists of striated muscle fibers, measuring 70 ^ in 
length and 10 to 15 fi in width, and characterized by an absence of 
sarcolemma and by the fact that they branch and anastomose. A 
few non-striped cells exist in the endocardium and valves. 

The heart is lined by a serous membrane, the endocardium, 
consisting of a surface endothelium supported by fibrous and elastic 
connective tissue. Like the cornea, the endocardium is devoid of 
blood-vessels; this is also true of the semilunar valves. In the 
auriculo-ventricular valves vessels extend to within a short distance 
of the free edge. The lymphatic vessels likewise do not reach to 
the border of the valves. 

The heart is nourished through the coronary arteries, which are 
filled during systole. It is during the heart's contraction that the 
capillaries are dilated, and therefore best prepared to receive the 
blood supply. 



^ 




pp w 



Hypertrophy. — This is a common condition, and is generally 
a consequence of an increase in the work of the heart. From an 
anatomic standpoint, five kinds of hypertrophy may be distin- 
guished. (Figure a represents the normal heart.) 

1. Concentric hypertrophy. (Fig. 1.) This is exceedingly rare, 
and is characterized by a diminution in the cavity of the heart and an 
increase in the thickness of the wall. 

2. Simple ', or pure hypertrophy. (Fig, 2.) In this the cavity is 
of normal size, but the muscular wall is thickened. It is a transitory 
stage, rarely seen at autopsy. 

3. Hypertrophic dilatation. (Fig. 3.) This is the commonest 
form of hypertrophy — the wall is increased in thickness and the 
cavity is enlarged. 

4. Dilated hypertrophy. (Fig 4.) This is a further stage, and 
is characterized by dilatation of the chamber, with a muscular wall 
which is thinner than that of hypertrophic dilatation, being about 
the thickness of the normal muscle. 

5. True dilatation. (Fig. 5.) The cavity is enlarged, and the 
wall is thinner than normal. Since the muscular wall has to sur- 
round a very large cavity, there is even here some hypertrophy. 



THE HEART. 131 

From the functional standpoint we may divide hypertrophies 
into the sufficient and the insufficient. The first four varieties may 
be sufficient, the last three insufficient. The first two are always 
sufficient ; the fifth is always insufficient. The possible insufficiency 
of the third and fourth is due to degenerative changes in the cardiac 
muscle. 

The hypertrophy, although it affects to a certain extent all 
cavities, is not uniform, but usually involves one cavity more than 
the others — as a rule, the left ventricle. The auricles may be hyper- 
trophied, generally in association with ventricular hypertrophy. 

When the left ventricle is hypertrophied the heart preserves its 
shape, but is lengthened downward in the direction of the apex. 
When the hypertrophy is in the right ventricle the heart becomes 
globular in outline. Dilatation also imparts to the heart a globular 
shape. 

Histologically, the hypertrophy affects all the structures of the 
heart. In the muscle the hypertrophy is chiefly numerical, but 
there is also a slight degree of simple hypertrophy. 

Etiology. — I. Mechanical interference from without, as pres- 
sure from an adherent pericardium or from tumors. The hyper- 
trophy is not marked, and is soon succeeded by atrophy. 

2. Mechanical defects in the valvular apparatus. The hyper- 
trophy involves different chambers according to the seat and nature 
of the valvular lesion. 

The greatest hypertrophy is seen in obstruction and insuffi- 
ciency of the aortic valve. The heart may weigh 1000 grams or 
more. The left ventricle is especially affected. 

3. Disturbances of the general circulation, increasing the resist- 
ance against which the heart has to pump, (a) Arterio-sclerosis ; 
(b) aneurysm. 

4. Disturbances of the pulmonary circulation, (a) Congenital 
defects ; (b) diseases of the lung, as emphysema, fibroid phthisis ; (c) 
disturbances in the pulmonary circulation from disease of the left 
side of the heart. In all of these the right ventricle is especially 
hypertrophied. 

5. Idiopathic causes, as nervous palpitation (exophthalmic 
goiter); exercise. The latter cause, i. e., exercise, might also be 
classified under disturbances of the general circulation. 

Causes of dilatation. Although in hypertrophy the coronary 
arteries share to a certain extent in the enlargement, becoming 



132 NOTES ON PATHOLOGY. 

longer and wider, the increase in size is insufficient to supply the 
heart with blood. At the same time, the coronary veins empty 
themselves with difficulty into the right auricle, and the blood is 
dammed back in the heart. There is generally also a sclerotic 
process in the coronary arteries diminishing their caliber. All 
these causes favor degeneration of the heart muscle and consequent 
dilatation. Hypertrophy, we may therefore say, always carries 
the danger of dilatation with it. 

Atrophy. — The heart becomes smaller, darker, and firmer; 
the pericardial vessels are prominent and tortuous, the endocardium 
and pericardium thickened. 

Causes, (i) Continued pressure, as from pericardial adhesions. 
(2) Senility. (3) Starvation. (4) Constriction of the auriculo- 
ventricular orifice, causing a relative atrophy of the corresponding 
ventricle. (5) Passive congestion. (6) Sclerotic endocarditis, with 
extension of the sclerotic process to the heart. This acts analog- 
ously to pericardial adhesions. (7) Congenital hypoplasia, as in 
some cases of chlorosis. 

Brown atrophy is the result of long-continued passive conges- 
tion. Pigment granules are deposited about the poles of the muscle 
nuclei ; the connective tissue is hyperplastic. 

Infiltrations.— 1. Fatty. This takes place between the 
muscle fibers and occurs in obesity and in pernicious anemia. It 
may lead to fatty degeneration by pressure on the fibers. 

2. Pigmentary infiltration — in cyanotic atrophy ; after hemor- 
rhages. The pigment is deposited about the poles of the nuclei. 

3. Calcification is most common in the valves ; it may occur 
at the auriculo-ventricular rings, and between as well as in the 
muscular fibers. 

Degenerations. — 1. Amyloid degeneration affects the con- 
nective tissue of the blood-vessels. 

2. Fatty degeneration is the most important degeneration. It 
begins as cloudy swelling, especially when due to acute conditions, 
as fevers or acute anemias. The muscle is softer, friable, slightly 
opaque, brownish or yellowish-brown in color. The process is best 
marked just beneath the endocardium of the left ventricle, where it 
presents itself as pale yellowish striae. At times the fatty degen- 
eration is uniform. In some cases it produces no change in color. 

Microscopy. The muscle fiber becomes filled with fine granules 
which are albuminous at first and obscure the striation. They are 



THE HEART. 133 

soluble in acetic acid. Later they become fatty, arranging them- 
selves in longitudinal rows, parallel with the axis of the fiber. 
Finally, the whole fiber passes into fat. 

Causes. (1) Poisons — chloroform, phosphorus, arsenic. (2) 
Toxins of acute infectious diseases. (3) General anemia. (4) Dis- 
turbances of the cardiac circulation, usually from excessive hyper- 
trophy. In great enlargement the heart never completely empties 
itself, hence, the capillaries are never perfectly filled ; the veins also 
are not fully emptied ; and in addition we have the sclerosis of the 
coronary arteries. 

3. Waxy degeneration. This is a form of hyaline degeneration 
at times met with in infectious diseases, particularly in typhoid and 
typhus fever. The muscle fibers first suffer cloudy swelling, then, 
instead of passing to fattv change, become opaque and waxy. In 
other instances, in these fevers, we have the ordinary fatty degen- 
eration. 

4. Hyaline degeneration is seen in the connective tissue of the 
arteries in old age ; it may attack the capillaries in acute infectious 
diseases. 

Circulatory Disturbances. — I. Hyperemia and anemia. 

2. Embolism and thrombosis. Thrombosis is more common 
than embolism, being favored by atheromatous changes in the 
coronary arteries. Emboli lodge most frequently in the anterior 
coronary artery. Both processes lead to infarction, either hemor- 
rhagic or anemic, generally the latter. The infarct softens (myo- 
malacia cordis, or cardiomalacid) and, if extensive, the heart may 
rupture. If rupture does not occur, the infarct is replaced by a 
scar ; the latter may yield and give rise to an aneurysm. 

Inflammation— Myocarditis.— Parenchymatous degener- 
ation (cloudy swelling) which occurs in acute infectious diseases, is 
sometimes termed parenchymatous myocarditis, but should only be 
so considered when accompanied by the vascular changes pertaining 
to true inflammation. 

Suppurative myocarditis is secondary to suppuration elsewhere 
in the body. We may have a single large abscess or many small 
abscesses. Causes. (1) Extension from neighboring structures, as 
the pericardium or the endocardium. (2) Septic embolism. 

The possible results are the same as in cardiomalacia from 
infarction. 



134 NOTES ON PATHOLOGY. 

Interstitial myocarditis, (i) This may be localized, the result 
of a regenerative process following abscess, infarct, or wound of the 
heart. (2) It may be diffuse, being a part of a general sclerotic 
process affecting the entire vascular system. (3) It may be due to 
extension of chronic inflammation from the endocardium or peri- 
cardium. 

As a result of the chronic inflammation the muscle fibers are 
pressed upon and atrophy — we may then have rupture of the heart 
or the formation of an aneurysm. 

THE ENDOCARDIUM. 

Endocarditis is of three varieties : (a) verrucose, of warty ; (6) 
ulcerative, and (c) sclerotic. The first two are acute, the third often 
begins acutely, but pursues a chronic course. 

(a) Warty endocarditis affects especially the left side of the 
heart, attacking the mitral and aortic valves with nearly equal 
frequency. The valve, particularly at the " line of contact," loses 
its luster and becomes somewhat thickened and granular in appear- 
ance, or it may be the seat of a number of warty projections. 
From the line of contact the process may extend along the valve 
to the endocardium of the heart or, in the case of the aortic valve, 
to the intima of the aorta. 

The process begins with a rapid formation of fibrin, which in 
the first place results from a coagulation necrosis of the endothelial 
cells and the fluid exudate from the valve. There is also a prolifer- 
ation of the endothelial and connective tissue cells leading to a 
round cell infiltration of the base of the projections. Secondarily, 
there is a deposit of fibrin from the blood upon the roughened 
surface. This deposit is somewhat laminated and can readily be 
removed. 

Terminations, (a) Resolution, (b) Organization of the cellular 
exudate and scar-formation. 

Etiology. It is probable that bacteria are always the cause of 
warty endocarditis, although none are found as a rule, very likely 
because the cases are examined long after the process has started. 
The disease can be produced by the injection of certain micro- 
organisms which are the same as those causing ulcerative endocar- 
ditis. A comparison may be drawn between warty endocarditis 
and croup, on the one hand, and ulcerative endocarditis and 



THE ENDOCARDIUM. 13S 

pharyngeal diphtheria, on the other. In warty endocarditis, as in 
croup, the process is superficial ; while in ulcerative endocarditis 
and in pharyngeal diphtheria, it is deep. 

The disease occurs at all ages, and most frequently in males, 
involving, in the order of frequency, the mitral, aortic, and pulmo- 
nary valves. The most common causes are rheumatism, chorea, 
and infectious diseases, as pneumonia and diphtheria. 

(3) Ulcerative \ destructive, diphtheritic, or malignant endocarditis. 
(The name mycotic was applied at a time when the warty form was 
considered not to be of bacterial origin.) 

Macroscopy. The naked-eye appearance varies from a simple 
opacity and slight roughness to the most extensive destructive pro- 
cess. We find excavated ulcers, with ragged edges ; perforation 
of the valves ; acute aneurysms of the valves or the heart wall ; 
abscesses ; involvement of the heart itself. 

Four varieties are distinguishable: (1) Endocarditis polyposa. 
In this the deposit of fibrin is abundant and forms polypoid masses. 
(2) E. villosa — a name given when the projections are small. (3) 
E. ulcerosa — when ulcers are present. (4) E. pustulosa is applied 
when there are small abscesses. The process begins at the line of 
contact of the valves and extends to the base, and thence in the 
direction of the circulation, as, e. g., from the anterior mitral leaflet 
to the aortic valve, and from this to the intima of the aorta. 

Embolism is common, particularly in the skin, where it leads 
to hemorrhages. 

Microscopy. We have the formation of a granulation tissue 
which has a tendency to undergo coagulation and liquefaction 
necrosis. The large accumulation of round cells in a valve deficient 
in blood-vessels and having but little connective tissue, can only be 
accounted for by a cell-formation from dormant cells (Schlummer- 
zellen) y the stimulus to which is given by the micro-organisms. 
Dense masses of bacteria are present in the affected area. Besides 
the evidences of necrosis we find minute hemorrhages in the valves 
from the rupture of newly-formed blood-vessels. 

Etiology. The causes are as a rule the ordinary pyogenic 
micro-organisms, especially staphylococcus pyogenes aureus and 
streptococcus pyogenes ; the pneumococcus and the gonococcus 
have also been found. 

How do the micro-organisms reach the heart ? In some cases 
the disease is secondary to a pyogenic process elsewhere in the 



136 NOTES ON PATHOLOGY. 

body, but usually it is a primary affection, engrafted, in the majority 
of cases, upon a valve the seat of chronic endocarditis. The micro- 
organisms are probably brought in the general circulation and not 
by the branches of the coronary arteries. The latter sometimes 
happens, however, the embolus lodging at the base of the valve, 
where the process then begins. 

The line of contact is especially subject to lesions, and as a 
rule the bacteria are first deposited there from the blood passing 
over the valve. 

(c) Sclerotic endocarditis. This may be (a) a local regenerative 
process, either the formation of a scar, following wound, abscess, 
or infarct of the heart, or the final step in the other forms of endo- 
carditis. More commonly it is (b) a primary chronic inflammation, 
progressive in character, with an attempt to form new connective 
tissue. It occurs as a part of a general sclerosis affecting the 
arterial system and certain organs, as the liver and kidney, and is 
not confined to the valves but may involve the endocardium of any 
part of the left ventricle. 

Macroscopy. The appearance varies from a slight thickening 
and bulging at the line of contact or on the body of the valve, to 
enormous thickening, contraction, and puckering of the valve, with 
constriction of the ring in which it is inserted. 

These changes bring about the ordinary valvular heart disease, 
the lesions being such as either cause obstruction or insufficiency of 
the valves. 

The papillary muscles and chordae tendinese may also be 
greatly thickened. 

Microscopy. The structural changes depend upon the forma- 
tion of granulation tissue in the fibrous layer of the endocardium. 
The newly-formed blood-vessels as well as any pre-existing ones 
are the seat of proliferation (in the intima) and become obstructed. 
As a result of the malnutrition the new tissue undergoes fatty 
degeneration, the affected area becoming yellowish-white. This 
degeneration is termed atheroma. When calcification occurs in the 
fatty area an atheromatous plate is produced. The degenerated 
tissue may also break down into an emulsion, which may be dis- 
charged into the blood, an atheromatous ulcer remaining. 

Sclerotic endocarditis affects especially the left side of the 
heart, and to a certain extent seems to be physiologic in old age. 



THE BLOOD-VESSELS. 137 

Rupture of the heart occurs most commonly in the center or 
toward the apex of the left ventricle. The causes are infarcts, 
abscesses, interstitial myocarditis, aneurysm, and traumatism. 

Tumors. The primary tumors are fibroma, lipoma, and rhabdo- 
myoma. Among secondary tumors, which are more frequent, we 
have sarcoma, especially melanotic, and carcinoma. 

Malformations. The most frequent are defects in the septa, 
usually a patulous condition of the foramen ovale ; at times also 
imperfection in the interventricular septum. Fenestration of the 
valves is not rare and is apparently an attempt at the formation of 
chordae tendineae in the semilunar valves. We may have constric- 
tion of the large vessels, especially the pulmonary artery. 

Valvular lesions of the right heart are often met with at birth. 
They are not to be considered malformations, but as the results of 
endocarditis during intrauterine life, during which the right heart 
has the most work to perform. 

Tuberculosis is rare in the heart. It may be miliary, affecting 
the endocardium of the right side especially, or it may be a caseous 
tuberculosis, the result of extension from neighboring organs 
through the pericardium. 

Syphilis. Gummata are met with but are rare. 



THE BLOOD-VESSELS. 

An artery has three coats — the intima, the media, and the 
adventitia. The intima consists of an internal layer of long endo- 
thelial cells arranged longitudinally ; outside of this is a delicate 
fibrous connective tissue containing stellate cells — the sub endothelial 
layer. The outermost part of the intima is made up of elastic 
tissue, appearing in transverse section as a distinct corrugated mem- 
brane, the internal elastic membrane. In the larger vessels this is 
fenestrated. The media consists chiefly of unstriped muscular 
tissue. The adventitia is made up of areolar and fibro-elastic tissue, 
and is the most resistant of the three coats. 

Functions. 1. Arteries are channels for the blood, but by 
reason of their contractile property, which is under the influence of 
the nervous system, they control to a large extent the amount of 
blood passing through them. The demand of the organ receiving 
the supply has much to do with the variations in caliber. 



138 NOTES ON PATHOLOGY. 

2. The endothelial cells have specialized properties ; they are 
not merely filtering-cells, but have what might be termed a selective 
action. 

The Pulse* — In a pulse-tracing taken with the sphygmograph, 
three main waves are recognizable. The first, the inertia, or per- 
cussion wave, ordinarily the highest, is due to the ascent of the lever, 
which, by the sudden impulse given to it, is carried beyond the point 
which it would reach if it were merely lifted by the gradual dilata- 
tion of the artery. After the lever has fallen, it is again lifted by 
the true expansion of the artery, produced by the influx of the 
blood — this gives rise to the second, or tidal wave. The third wave 
is due to the closure of the aortic valve, and is known as the recoil, 
or aortic wave. The remaining portion of the tracing is termed the 
wavy remainder, and is made up of a number of small, secondary 
waves. 

When the artery is yielding, in other words, when tension is 
low, as in fevers, all waves are well marked; when the artery 
is tense — high tension — the first wave may be absent, the apex being 
flat. In aortic insufficiency, the recoil, or aortic wave is absent. 

Diseases of the Arteries. Hypertrophy occurs (a) in 
the establishment of collateral circulation ; (b) in conditions of 
excessive blood-pressure. 

Atrophy. — Atrophy of arteries is seen (a) in atrophic organs, 
(d) in the stumps remaining after amputation, (c) in conditions of 
wasting, as, e. g., in tuberculosis. But while the general emaciation 
in tuberculosis may account in part for the atrophy, it is probable 
that there is often an under-development of the large vessels in 
persons susceptible to the disease. 

Infiltration. — Calcification occurs in the intima and media 
as a frequent part of the atheromatous process, being preceded by 
fatty degeneration. It presents itself as minute granules in the 
fibrillar layer of the intima and in the connective tissue and, at 
times, in the muscle cells of the media. 

Degenerations. — I. Amyloid degeneration is most common 
in the smaller arteries, affecting first the connective tissue of the 
media. In the larger vessels it occurs in the intima and media. It 
is most frequent in the glomeruli of the kidney. 

2. Fatty degeneration. This is very common and involves the 
fibrillar layer and endothelium of the intima; in the media the 



THE BLOOD-VESSELS. 139 

muscle cells are affected. To the naked eye it presents itself as 
opaque whitish patches. 

Causes, {a) Poisons — as phosphorus ; chloroform, (b) Acute 
infectious diseases, (c) Sclerotic arteritis, in this giving rise to the 
process termed atheroma, (d) Poisons the result of faulty meta- 
bolism. 

3. Hyaline degeneration. This is a frequent process, being an 
early stage of arterio-sclerosis. It affects the connective tissue, 
first of the intima, then of the media, causing in the latter atrophy 
and disappearance of the muscle cells. In the capillaries it appears 
as minute, glassy, shining beads or globules just outside of the en- 
dothelium ; in the larger vessels it produces a homogeneous appear- 
ance. As a local process it is common in the ovary. Hyaline 
material stains well with eosin. 

Causes, (a) It is a part of the atheromatous process, preced- 
ing fatty degeneration, (b) It may be produced acutely by infectious 
diseases. 

Inflammations. — I. Acute purulent arteritis. This corre- 
sponds to the pustulous form of ulcerative endocarditis. Its causes 
are (a) extension from without, which gives rise to periarteritis, (b) 
septic embolism or thrombosis, leading to an endarteritis, (c) in the 
aorta, extension of the suppurative process from ulceration of the 
endocardium. 

2. Acute productive arteritis, thrombo-arteritis , or obliterating 
endarteritis. This is analogous to verrucose endocarditis. It begins 
in the intima, but may extend to the other coats, and is character- 
ized by the formation of new connective tissue. As a rule it is 
started by a thrombus, into which, as a framework, the newly- 
formed tissue and blood-vessels project, the process usually termi- 
nating in complete obliteration of the artery. This at least is true 
of the smaller arteries. In the larger vessels there is generally not 
complete occlusion, but only a patch on one side or an annular con- 
striction. New vessels permeate the thrombus in about twelve 
days after its formation. 

The best example of thrombo-arteritis is that following ligation 
of arteries. 

Obliterating endarteritis is seen in the healing of arteries in 
wounds, after ligation, after occlusion of arteries by non-specific 
emboli, and in organs the seat of great hyperplasia of the connec- 
tive tissue, as in cirrhosis of the liver or the kidney. 



140 NOTES ON PATHOLOGY. 

3. Sclerotic endarteritis^ or arteriosclerosis. This is comparable 
to sclerotic endocarditis, and gives rise to a gradual thickening of 
the intima, either diffuse or circumscribed. The diffuse form is to 
a certain extent physiologic in advanced life. The localized form 
causes circumscribed swellings of the intima which are at first 
translucent, later firmer and opaque, and yellowish-white in color, 
and become visible to the naked eye as plates. Still later the 
patches become infiltrated with lime, or they may break down 
and discharge into the artery leaving ulcers. 

In the stage of translucency we have hyaline degeneration of 
the intima ; the opacity and the yellowish-white color are due to 
fatty degeneration (cholesterin plates may be deposited) ; the harden- 
ing is due to calcification ; the breaking-down to liquefaction necrosis. 
The ulcer may become the seat of thrombosis — a thrombo -arteritis 
follows, with eventual cicatrization of the ulcer. 

As a rule we find all the processes going on in the arteries 
at the same time. 

It is customary to term arterio-sclerosis atheroma ; this is not 
correct since atheroma defines only one stage of the process, viz., 
the fatty degeneration, and leaves out of consideration the inflam- 
matory element. 

Microscopy. The process begins in the fibrillar layer of the 
intima, close to the media, and gives rise to a very marked swelling 
of the inner coat, usually on one side of the artery. Hyaline 
degeneration sets in and causes a disappearance of the nuclei, the 
affected region becoming homogeneous. As the process advances 
minute granules appear in the area — some are fatty in nature, others 
albuminous. They are the result of a degeneration, either of the 
hyaline material or of the cells spared by the hyaline change. The 
hyaline material now breaks up into lamellae. As the disease pro- 
gresses there is a tendency for the accumulation of fatty detritus in 
certain large areas, often with the deposit of cholesterin plates. 
These areas appear as yellowish spots visible to the naked eye. 
They finally break down and are discharged into the lumen of the 
vessel, leaving the so-called atheromatous ulcers. 

In addition to these degenerative changes the process of arterio- 
sclerosis presents as a very important feature, evidences of prolifera- 
tion of the connective tissue. We find an accumulation of round 
cells about the degenerated area ; new blood-vessels, coming from 
the vasa vasorum, are seen to push into the round cell infiltration 



THE BLOOD-VESSELS. 141 

in the intima. The media and adventitia are also the seat of cell 
proliferation, with the production of dense fibrous tissue. The vasa 
vasorum of the adventitia are involved in the sclerotic process — 
the diminution in the blood-supply thereby produced, accounts in 
part for the degeneration of the wall of the blood-vessel. 

As a rule the cell proliferation in the intima does not succeed 
in forming new connective tissue, although this may occur in syphi- 
litic sclerosis. 

Sclerosis is common in advanced life. It is more frequent in 
certain sections of the country than in others ; it is, for instance, 
more marked along the coast of North and South Carolina than 
elsewhere ; perhaps this is connected with an excessive use of fish 
as food (Professor Guiteras). The negro race is especially liable to 
sclerosis. 

Pathogenesis. The process begins in one of two entirely 
different ways. 

(a) It is a primary process of degeneration of the arteries, such 
as we find in other organs, being the result of the action of poisons, 
as alcohol and the infectious diseases. It may, for example, follow 
measles or scarlet fever, especially when either occurs in advanced 
life. The poison produces a hyaline degeneration of the vessel ; this 
is then followed by the other degenerative changes. As the degener- 
ated material requires removal, an inflammatory process is developed. 

(J?) The process may originate from minute tears in the vessels 
the consequence of a loss of elasticity. It has been found, especially 
by Thoma, that arteries lose their elasticity before they show 
sclerosis. If we examine the arteries from a body in which there 
is sclerosis of the aortic arch, we may find neither macroscopic nor 
microscopic changes in the other arteries, although it was, a priori, 
to be supposed that they should present an earlier stage of the pro- 
cess. We can demonstrate, however, a functional change — the 
arteries stretch more readily than normal vessels. 

The loss of elasticity is as yet not explained, but as a result of 
it we very likely have minute tears in the intima, or in the connec- 
tive tissue of the media, due to sudden changes in pressure. In 
these tears the inflammatory process is started. It extends to the 
vasa vasorum, leads to defective blood-supply of the arterial wall, 
and, secondarily, to degeneration. 

The loss of elasticity is in the early stages compensated for by 
an hypertrophy of the muscular coat, which, together with the 



142 NOTES ON PATHOLOGY. 

hyperplasia of the connective tissue, leads to an increase in the 
resistance to the circulation. The last manifests itself, clinically, 
as high arterial tension, and gives a characteristic pulse-tracing. 

Seats. The process is most marked in arteries subject to 
sudden changes in pressure, in those not well protected, and in 
those with but few branches. Most frequently affected are the 
arch of the aorta, the thoracic and abdominal aorta, the splenic, 
iliac, femoral, and coronary arteries, and the vertebral inside of the 
cranium. The pulmonary and mesenteric arteries are very rarely 
the seat of sclerosis. 

Causes. Among the clinical causes are named senility, alcohol, 
probably syphilis, rheumatism, gout, and heredity. 

Effects. The effects of sclerosis are narrowing or occlusion of 
the artery, rupture, aneurysm. 

Syphilitic Arteritis. — This may occur diffusely, affecting 
all the arteries of an organ, or locally, in the true syphilitic lesions, 
the gumma and chancre. It is characterized by a great proliferation 
of cells, without any marked tendency to degeneration. The intima and 
adventitia are especially affected ; the media remains passive, and 
degenerates in the later stages. In the intima and adventitia the 
process may go on to the formation of fibrous tissue. This form 
of sclerosis is not absolutely characteristic of syphilis, but if we 
find all the vessels of an organ so affected, we may infer, but 
not positively predicate, syphilis. The process is most common in 
the brain. The vessels appear like fibrous cords. 

The ordinary sclerosis with atheroma can, of course, also 
occur in a syphilitic subject. 

Tuberculous Arteritis. — This involves especially the ad- 
ventitia, being the result of extension from neighboring structures. 
We find tubercles in the adventitia, usually on one side only, with 
giant cells and cheesy degeneration ; the intima and media at the 
same level present a round cell infiltration. The effects of tuber- 
culosis are miliary aneurysms or, more commonly, erosion and 
rupture of the arteries. 

Periarteritis Nodosa. — This is rare and not well under- 
stood. It gives rise to the appearance of nodules on the adventitia, 
which are either inflammatory masses or minute aneurysms filled 
with clots. The mesenteric and muscular arteries are the seats of 
the process. 



ANEURYSM. 143 



ANEURYSM. 



An aneurysm is a circumscribed dilatation of a blood-vessel. 
There are three varieties of aneurysms : (1) the ectatic, (2) the 
saccular, and (3) the dissecting. 

(1) Ectatic aneurysm. This is simply a dilatation of the vessel, 
the wall consisting of all the arterial coats. Three forms are 
described: (a) the fusiform; (b) the cylindrical,, and (c) the cirsoid. 
In the last the dilatation goes around the vessel in a spiral manner. 

(2) Saccular aneurysm. This is a localized dilation of the 
vessel wall and consists of a sac communicating with the vessel by 
a narrow neck. 

Varieties, (a) True — one consisting of all the coats of the 
-vessel, (b) False — one in which one or more of the coats are 
absent, the wall being usually made up of the adventitia, or part of 
it, and newly-formed connective tissue. 

True saccular aneurysm may be single or miliary, the latter 
being common in the vessels at the base of the brain. 

Varieties of false aneurysm, (a) Simple. This is the most 
frequent form and consists of a sac made up of adventitia or of newly- 
formed tissue, or of both. 

(0) Varicose aneurysm. This is an aneurysm communicating 
with a vein. 

(y) Aneurysmal varix. This is produced by the opening of an 
artery into a varicose vein. The latter pulsates. 

(3) Arterio-venous aneurysm. In this we have a simultaneous 
injury of an artery and a vein, the blood from both being poured 
into the surrounding tissues. 

(3) Dissecting aneurysm. This is produced by a rupture 
of the inner coats of an artery, the blood finding its way between 
the intima and adventitia. After separating the tunics for some 
distance, the blood breaks either through the inner coat into the 
vessel, or outside into the surrounding tissues. Dissecting aneu- 
rysm is most common in the aorta, beginning at the junction of the 
ascending and transverse portions of the arch ; it generally dissects 
backward and ruptures into the pericardium. 

Causes Of Aneurysms.— (i) Arterio-sclerosis with athe- 
roma is the commonest cause. (2) Inflammatory processes affect- 
ing the arteries from the outside, as tuberculosis. (3) Changes 
within the vessels, as embolism. This is sometimes the cause of 



144 NOTES ON PATHOLOGY. 

splenic aneurysm, although it is probable that the walls of the 
artery are primarily diseased. The embolus may be a parasite, as 
in aneurysm of the mesenteric arteries of the horse. (4) Traumat- 
ism — this usually causes a false aneurysm. 

Changes produced by aneurysms. Prominent are the pressure 
symptoms. Pressure in the early stages causes hyperplasia, later 
atrophy, of the surrounding structures. This is seen best in bones, 
as the sternum, ribs, or vertebrae. 

Healing of an aneurysm is not common. Thrombosis is fre- 
quent in the sac, but the space to be filled is so large that occlusion 
is not successful as long as the sac communicates with the artery, 
owing to the constant current of the blood. After ligation, healing 
may take place, the clot becoming organized by a process of 
thrombo-arteritis. 

Seats, (a) Of large aneurysms : arch of the aorta, popliteal 
and femoral artery, abdominal aorta, carotid and subclavian artery. 
(5) Of miliary aneurysms : the vessels at the base of the brain, the 
pulmonary arteries. 

The Veins. — The veins present changes analogous to those 
found in arteries, but being more elastic and yielding, and less subject 
to sudden distention, they are less liable to sclerosis. 

Phlebitis. Suppurative Thrombo-phlebitis.— Acute 

inflammation of the veins is generally suppurative, and is the result 
of extension of suppuration from neighboring organs. The peri- 
vascular lymph spaces are first involved, the process extending from 
them to the veins. A thrombus forms within the vein ; as it softens, 
emboli are carried in the circulation and produce pyemia. 

Phebeotasia, Varix, or Varicose Veins. — This varies 
from slight to very marked degrees of dilatation. The vessels be- 
come elongated and tortuous, and small veins become prominent ; 
the walls are thickened, and there is also a hyperplasia of the sur- 
rounding connective tissue. 

Causes. 1. Mechanical disturbances in the venous circulation, 
as pressure from without (tumors), inflammation of the walls, throm- 
bosis. 

2. Failure of the cardiac circulation, the result of the degenera- 
tive processes of advanced life. This may not be sufficient until 
aided by a slight local disturbance in the veins. 



THE VEINS. 145 

3. Want of muscular exercise, favoring especially varicose 
veins of the lower extremities. 

4. Gravity — this is a factor in varix of the lower parts of the 
body. 

5. Some congenital defect in the walls of the veins, a condition 
that may be transmitted in families. 

6. Race. The white race is more often affected with varicose 
veins than the colored. 

Seats. Varix is most common below the bifurcation of the 
two common iliacs, and may involve, particularly when due to intra- 
pelvic pressure, the veins of the broad ligament, labia, bladder, and 
prostate, the spermatic veins, the hemorrhoidal veins, and the veins 
of the lower limbs. 

Hemorrhoids , or piles, are produced by general disturbances in 
the circulation, by pressure of pelvic tumors, by cirrhosis of the liver, 
and by constipation, and in structure differ somewhat from ordinary 
varicose veins. In the latter we have dilated parts with intervening 
healthy tissue ; in hemorrhoids the dilatations are so close together 
as to resemble cavernous angioma. Septic infection about hemor- 
rhoidal veins is common ; tuberculous abscesses may form and lead 
to fistulae. 

Complications of varix. (1) Rupture and bleeding, especially 
in the case of hemorrhoids. (2) Inflammation about the veins, 
either chronic with thickening, or acute. The thickening may give 
rise, in the lower extremities, to varicose elephantiasis. In associa- 
tion with this, and also without it, we may have varicose ulcers. 
(3) Thrombosis is common — it may lead to thrombo-phlebitis. The 
clot may become infiltrated with lime and constitute a phlebolith, or 
veinstone. 

Tumors. Both arteries and veins may become involved from 
the outside ; sarcoma is especially apt to grow along the blood- 
vessel. 

If the tumor spreads from other tissues, it is much more apt 
to affect the veins than the arteries. This is seen very plainly in 
the portal vessels, where in certain cases the tumors can be observed 
to project into the lumen of the veins. Whenever there is metastasis 
to the lung from cancer of the stomach or liver, we find such pro- 
jections in the portal vessels. 

Phleboliths, or veinstones, are calcareous nodules formed in the 
interior of veins, and represent calcified thrombi. 
10 



146 NOTES ON PATHOLOGY. 

THE LYMPHATIC VESSELS. 

Lymphangitis and Perilymphangitis are the result either 
of extension or of embolism, and, pathologically, do not differ from 
inflammation of other vessels. 

Lymphectasia. — This is common in the lower extremities, 
especially in elephantiasis. It is also seen in the mesentery, where 
it gives rise to an appearance resembling miliary tuberculosis. The 
mesentery is dotted over with whitish nodules, which when cut 
exude a little fluid. Similar nodules are found in the lung and 
pleura, and are here the result of pressure upon the lymphatics by 
tumors or by an hypertrophied heart. The effects of the compres- 
sion may manifest themselves also in the liver, where the condition 
bears such a close resemblance to miliary tuberculosis that only the 
microscope can at times decide. 

Metastasis of cancer is common along the lymphatic vessels. 
Endothelioma is most frequent in serous cavities. The serous 
cavities are to be looked upon as huge lymphatic spaces. 



CHAPTER X. 



DISEASES OF THE NERVOUS SYSTEM. 

The weight of the brain is in man about 1350 grams, in woman, 
1220 grams. The brain is covered by three membranes, the dura, 
the arachnoid, and the pia. The dura consists of an outer periosteal 
and an inner serous layer. In children it is adherent to the cal- 
varium and has to be removed with it ; in adults it is normally 
unattached. The arachnoid is a delicate membrane which has 
no relation to the dura, but is connected with the pia by means 
of fibrous bands. It does not dip down into the sulci, but passes 
over them. The pia closely invests the entire surface of the brain 
and contains the blood-vessels nourishing the cortex. It dips down 
into the fissures, carrying the vessels with it. The relation of these 
vessels is indicated in the diagram, viz., from above downward, vein, 
artery, vein. Between the arachnoid and the pia is the subarachnoid 
space containing cerebro-spinal fluid. 



ANATOMY AND PHYSIOLOGY OF THE BRAIN. 147 

The blood-vessels of the brain are divisible into two groups, 
the cortical and the central or basilar. The former supply the 
cortex ; they are terminal vessels and are often the seats of embolic 
processes. The central arteries nourish the ganglia and other 
structures at the base of the brain. Being small and coming off 
directly from the large vessels of the circle of Willis, they are sub- 
ject to great pressure, and in consequence are often the seat of 
atheroma and miliary aneurysms, as well as of rupture. 

ANATOMY AND PHYSIOLOGY OF THE BRAIN. 

But few words can be devoted to this subject in this place. It 
should be recognized, however, that a study of diseases of the brain 
as well as the localization of lesions is impossible without a thorough 
knowledge of the anatomy and physiology of the organ. 

The brain consists of the cerebrum, cerebellum, pons, and 
medulla oblongata, the last being, physiologically, a part of the 
spinal cord. The cerebrum, which chiefly concerns us, is made up 
of two symmetrical halves, each consisting, in a general way, of a 
cerebral mantle and basal ganglia. In the center of the brain we 
have a series of communicating cavities, the ventricles. The cerebral 
mantle is thrown into a number of folds or convolutions of which 
the most important are the following : the ascending frontal and 
ascending parietal, which constitute the main motor area ; the pos- 
terior extremity of the third left frontal convolution which together 
with the lowest portion of the ascending frontal represents the 
center for voluntary speech ; the occipital convolutions, particularly 
the cuneus, in which the center for psychic vision is situated ; the 
superior temporo-sphenoidal convolution, the center for hearing ; 
the uncinate gyrus, the -center for olfaction. 

At the base of the brain, projecting into the ventricles we have 
two important ganglia, the corpus striatum and the optic thalamus, 
the former being composed of two parts, the caudate nucleus and 
the lenticular nucleus. 

Projecting upward from the pons, and connecting the cerebrum 
with the remainder of the nervous system, is the crus cerebri, or 
cerebral peduncle. This enters the base of the brain and passes 
upward between the basal ganglia as the internal capsule. The 
internal capsule consists of an anterior and a posterior limb which 
join at an angle, termed the knee. The anterior limb is bounded 
on the outer side by the lenticular nucleus, on the inner, by the 



148 



NOTES ON PATHOLOGY. 



caudate nucleus. The posterior limb lies between the optic thala- 
mus on the inner, and the lenticular nucleus on the outer side. 
The lenticular nucleus is situated on a lower level than the other 
nuclei, and is, in a sense, covered over by the internal capsule, so 
that a horizontal section of the brain would first uncover the cau- 
date nucleus and optic thalamus, and on removing a portion of 
these, the internal capsule would be exposed. If the latter be 
folded toward the mesial surface like a flap, the lenticular nucleus 
comes into view. 

In the knee and the anterior two-thirds of the posterior limb 
of the internal capsule we find the motor fibers carrying impulses to 
the muscles of the opposite side of the body. The posterior third 
of the posterior limb gives passage to sensory fibers. 

The crus cerebri, the continuation of the internal capsule, con- 
sists of two chief parts, an upper, or tegmentum, carrying sensory 
fibers, and a lower, or crusta, composed mainly of the motor tracts. 

The upward expansion of the internal capsule is known as the 
corona radiata — it spreads out like a fan and goes to almost every 
part of the cortex. 

ANATOMY AND PHYSIOLOGY OF THE SPINAL CORD. 

The spinal cord has a covering corresponding to that of the 
brain, but the dura does not form the periosteum of the vertebrae. 




DISEASES OF THE MEMBRANES. 149 

In the white matter of the cord the following physiologically 
distinct tracts can be made out : 

1. Anterior or direct pyramidal tract (a). 

2. Lateral or crossed pyramidal tract (d). 

3. Postero-lateral tract, or column of Burdach (e). 

4. Postero-median tract, or column of Goll (/). 

5. Direct cerebellar tract (c). 

6. Antero-lateral or Gowers' tract (b). 

The lateral limiting tract is a narrow band of fibers bordering 
on the gray matter, between the anterior and posterior horns. 

The anterior and crossed pyramidal tracts are descending, or 
motor ; the tracts of the posterior column and the direct cerebellar 
tract are ascending, or sensory tracts. The antero-lateral tract is 
not well understood, but is supposed to be ascending in character. 

DISEASES OF THE MEMBRANES. 

Bone. — The skull should always be examined for tuberculous 
or syphilitic bone disease. The distinction between the two is 
difficult, but tuberculous lesions are generally funnel-shaped, with 
the widest part toward the periphery, and occur more frequently in 
the calvarium ; syphilis is more common at the base. At times 
the microscope alone will serve to determine the nature of the lesion. 

Dura. — 1. External ossifying pachymeningitis generally in- 
volves the bone as well as the outer layer of the dura, and is usually 
connected with tuberculous, syphilitic, or other inflammatory disease 
of the cranium. Osteophytes and exostoses are produced. 

2. Purulent pachymeningitis is due to pyogenic organisms 
which as a rule reach the dura by extension from neighboring 
parts, as the middle ear, or through wounds in the skull. 

3. Thrombosis is most common in the large sinuses, and is 
generally the result of extension of a suppurative process either 
from the bone (middle ear disease) or from the interior of the brain. 
The clots may soften and lead to pyemia. 

The lesions of the internal layer of the dura are the following : 

1. Tumors. Tumors are more frequent in the dura than in 
other parts of the brain, sarcoma being the most common form. 

2. Syphilis — gummata. 

3. Tuberculosis — tubercles. 

4. Internal ossifying pachymeningitis. This is an inflammation 
affecting especially the falx cerebri, the newly-formed tissue being 



IS© 



NOTES ON PATHOLOGY. 

Brain. 



Bone 



Tumors ) 
Syphilis VDura 
Tuberculosis J 



Ext. Ossifying Pachymeningitis 



Purulent 

Pachymeningitis 

Thrombosis 



Int. Ossifying 
Pachymeningitis 



Internal Hemorrhagic 
Pachymeningitis 



Inter-Meningeal 
Hemorrhage . 



Hematoma 
Hygroma 

No Exudative Process on Arachnoid 



Arachnoid « 
Edema 



Pia. 



Vacuum 
Dropsy 



Acute Arachnitis I 
or 

Leptomeningitis ] 

1. Cortical I 1. Serous 

2. Basilar | 2. Purulent 



■Vein 

■Artery 

-Vein 



Chronic Arachnitis 
or Leptomeningitis 



leptomenmgi 
Superficial) 

1. Fibrous 

2. Ossifying 

3. Pacchionian 

and 

(Deep) 

or 



Encephalo-Meningitis, or 

Progressive 

Paralytic Dementia 



Vertebral 



Cord. 



Periostitis 
Extra-Meningeal Abscess 

External Pachymeningitis 



Dura 



Arachnoid 
and Pia 



Internal Pachymeningitis 
Spinal Meningitis— Leptomeningitis 



| Meningo-Myelitis 



Cord 



DISEASES OF THE MEMBRANES. 151 

converted into bone by metaplasia. When evidences of inflam- 
mation are absent, the bony plates might be considered to be 
osteomas. 

5. Internal hemorrhagic, or fibrinous pachymeningitis. This is 
a chronic inflammation, with subacute exacerbations, in which 
patches of delicate connective tissue form on the inner surface of 
the dura. New blood-vessels project into the tissue ; their rupture 
gives rise to hemorrhages, the blood being held in the meshes of 
the new connective tissue. The condition is circumscribed, often 
symmetrical, affecting especially the parietal and occipital regions. 

6. Intermeningeal hemorrhage. This is due to rupture of veins 
passing from the pia to the sinuses. Its causes are either direct 
injury from the outside or indirect trauma, as concussion. It is 
usually diffuse and may extend down to the base. 

7. Hematoma is a blood tumor resulting either from hemor- 
rhagic pachymeningitis or intermeningeal hemorrhage. 

8. Hygroma is the clear cyst left after the absorption of the 
pigment from a hematoma. 

The Arachnoid. — This differs from other serous membranes 
in having no exudative processes upon its surface, except in the 
rare cases of penetrating wounds. 

Edema of the membranes. The fluid is in the subarachnoid 
space, especially in the region of the occipital lobes. The causes 
are (a) valvular heart disease, (b) Bright's disease, (c) inflammations 
within the cranial cavity, (d) pressure of tumors. A certain amount 
of edema occurs frequently during the agonic period. 

Vacuum dropsy is a localized serous effusion due to atrophy 
or aplasia of a part of the brain. 

Inflammations. From the pathologic standpoint it is not 
possible to separate the arachnoid and pia, and we consider inflam- 
mation of the two together under the head of leptomeningitis. 

(a) Acute leptomeningitis is either sero-fibrinous or purulent. 
Sero-fibrinous inflammation has to be distinguished from edema — 
opacity and the presence of flakes of lymph indicate the former, 
although a certain degree of opacity develops in long-standing 
edema. 

In the purulent we have a distinct accumulation of pus, espe- 
cially along the blood-vessels. 

Acute leptomeningitis is generally due to the ordinary forms of 
pyogenic micro-organisms, which reach the meninges either through 



152 NOTES ON PATHOLOGY. 

the blood or by extension ; or to the pneumococcus, the bacillus 
coli communis, or to other micro-organisms. 

The causes are epidemic cerebro-spinal meningitis, pneumonia 
(pneumococcus), malignant endocarditis, pyemia, typhoid fever, tu- 
berculosis, and other infectious diseases. Middle ear disease or 
brain abscess may cause leptomeningitis by extension. 

According to distribution we have cortical and basilar menin- 
gitis, though these are not distinctly separable. Epidemic cerebro- 
spinal and tuberculous meningitis affect principally the base. In the 
former the brain substance is also involved. There is also a syphi- 
litic basilar meningitis. 

Chronic leptomeningitis is of two varieties, the superficial, which 
affects the membranes alone, and deep, which involves also the 
brain — hence, the term, encephalo-meningitis, or peri-encephalitis. 

{a) Superficial leptomeningitis (a) Fibrous. In this we have a 
marked thickening of the pia-arachnoid, the result either of fre- 
quently repeated congestions and slight inflammation (especially in 
alcoholic subjects), or of certain forms of insanity. The mem- 
branes are opaque, (p) Pacchionian — This is either due to areas of 
localized inflammation, or consists in the formation of fibrous tu- 
mors, (y) Ossifying — This occurs in the late stages of fibrous 
leptomeningitis, as the result of metaplasia. 

(b) Deep leptomeningitis. This is a chronic inflammation in- 
volving the pia-arachnoid, and the gray and white matter of the brain, 
and is the anatomic basis of general paralysis of the insane. The 
disease usually has an acute beginning. Histologically, the process 
begins as an inflammation of the vascular apparatus and the neu- 
roglia, as evidence of which, in the acute cases coming under 
observation, we find a marked round cell infiltration of the peri- 
vascular spaces, the ganglion cells being healthy. The latter 
degenerate secondarily. 

DISEASES OF THE NERVE SUBSTANCE. 

Atrophy. — This is not promiscuously distributed, but is cir- 
cumscribed to definite parts, especially to the cells of the anterior 
horns of the spinal cord and the corresponding nuclei in the me- 
dulla. In the cord it gives rise to chronic anterior poliomyelitis, in 
the medulla to bulbar palsy. 

Microscopy. The ganglion cells lose their processes, become 
plumper, smaller, and pigmented. At times the cells are larger than 



DISEASES OF THE NERVE SUBSTANCE. 153 

normal, from a peculiar hyaline degeneration, and are vacuolated. 
The nerve fibers also degenerate ; the neuroglia is hyperplastic. 

The atrophy is progressive in character, extending gradually 
to neighboring groups. Atrophy also follows amputations in 
early life. 

Softening. — There is no sharp boundaiy line between soften- 
ing and inflammation. 

Causes of softening. 1. Hemorrhagic or anemic infarction. 

2. Gradual compression, as from tumors, disease, or displace- 
ment of the vertebrae. 

3. Traumatism, as a sudden crushing. 

4. Toxic agents, as the toxins of hydrophobia, tetanus, and 
other infectious diseases ; diabetes ; progressive pernicious anemia, 
and certain poisons introduced from without. 

The varieties of softening are the red, yellow, and white, the 
color depending upon the amount of blood present. In white soft- 
ening we have merely a fatty emulsion without blood. 

Microscopy. In softening, the archiblast suffers more than the 
parablast. The ganglion cells swell, become vacuolated, and lose 
their prolongations ; the nucleus ceases to stain, and the cells finally 
break down into a fatty detritus. The nerve-fibers undergo sim- 
ilar changes — the myelin breaks up into drops and appears beaded, 
and eventually is converted into fat granules. The axis cylinder is 
somewhat more resistant, but finally it degenerates also — it swells, 
becomes varicose, and breaks up into fatty granules which tend to 
run together. 

There is also an exudation of fluid which converts the fatty 
detritus into an emulsion. The neuroglia to a certain extent degen- 
erates also; but it may remain and hold the emulsion in its meshes. 

Accompanying the fatty degeneration we have distinct evi- 
dences of an inflammatory process, namely, the liquid exudate and 
a leukocytic infiltration. The wandering cells take up the fatty 
detritus, and become compound granule cells. 

Terminations, (a) Cicatrization — the neuroglia becomes hyper- 
plastic ; (b) cyst formation — the fatty debris is removed, a clear fluid 
being left. Such softening cysts are common in the brain. (c) 
Resolution. 

Secondary Degenerations. — These are circumscribed to 
certain tracts of fibers functionally allied, and hence, are called 



154 NOTES ON PATHOLOGY. 

systemic degenerations. They are due to lesions ol the trophic 
centers. Two kinds of secondary degenerations are described — 
the ascending and the descending. 

Ascending degeneration affects the posterior columns, especially 
the column of Goll,the direct cerebellar tract, and the ascending ante- 
rolateral tract. The trophic centers for the posterior column are in the 
ganglia on the posterior root ; those for the direct cerebellar tract, 
in the vesicular column of Clarke. Descending degeneration occurs 
in the anterior and the crossed pyramidal tracts, the trophic centers 
for which are situated in the motor area of the brain. 

Macroscopy. The affected areas are grayish in color and firmer 
than the healthy tissue. 

Microscopy. The changes are similar to those noted in 
softening, but there is much less fluid ; we have a slow, fatty 
degeneration, which is dry, because any fluid present is absorbed, 
and time is given for neurogliar hyperplasia. 

The degenerative changes begin within two weeks after sepa- 
ration of the fibers from their trophic centers ; they continue for 
two or three months ; then the neuroglia become hyperplastic. It 
is during the last stage that the cases generally come under obser- 
vation. These secondary degenerations affect the entire tract at 
the same time, and not that part nearest the trophic center first. 

Stained sections present two distinctly different appearances, 
according to the nature of the stain employed. When a nuclear 
dye like carmin is used, the affected area will be darkly stained, be- 
cause it contains an abundance of neuroglia cells. With a myelin 
stain, such as Weigert's hematoxylin method, the diseased parts 
appear pale, since they are deficient in myelin sheaths. By the use 
of either of these stains the affected areas can be distinguished 
with the naked eye. 

Primary Degenerations. — These like the secondary de- 
generations are also systemic, but are not due to lesions of the 
trophic centers. Two theories are held in regard to their etiology. 
According to the one the changes are primarily parablastic, i. e. } 
inflammatory; the neuroglia undergoes an excessive hyperplasia. 
The second assumes a primary degeneration of the archiblast, with 
a secondary hyperplasia of the neuroglia. Neither theory covers 
all cases; in some there is evidently a primary inflammation, 
affecting the blood-vessels and neuroglia, in others a primary 



PRIMARY DEGENERATIONS. 155 

degeneration of the ganglion cells, perhaps from poisons, followed 
by neurogliar hyperplasia or true inflammation. 

In a general way we may say that those lesions which are 
circumscribed to definite groups of cells functionally associated, 
are primarily archiblastic , as, e. g., amyotrophic lateral sclerosis and 
bulbar palsy ; while those which are distributed in irregular areas 
are primarily vascular, as, e. g., meningoencephalitis and multiple 
sclerosis. 

Some authorities are inclined to connect primary degenerations 
with tumors (those explained on Cohnheim's theory). There is a 
congenital tendency to degeneration of the ganglion cells, at times 
quite early in life, and this is followed by hyperplasia of the neu- 
roglia. Others claim that there is a congenital impulse to neu- 
rogliar hyperplasia, the degeneration of the nervous structure being 
secondary to this. 

Posterior sclerosis, Locomotor ataxia, or Tabes dorsalis. In this 
disease the primary degeneration is limited to the posterior columns, 
and has the character of an ascending degeneration. Its distribution 
varies — in the lumbar region the whole of the posterior column, 
especially the part nearest the posterior horn, is affected. A small 
rim in contact with the gray commissure usually escapes. In the 
higher parts of the cord the lesion is more median ; in the dorsal 
region there is generally a layer of healthy tissue between the 
affected postero-external and postero-median columns. In the 
cervical part of the cord only the column of Goll is affected. Ad- 
vanced cases show involvement of the entire posterior column. In 
the sclerosed portions amyloid bodies are often found. 

In addition to the cord lesion we have changes in the nerve 
tracts of the brain, as the optic tract and oculo-motor nerve, and 
trophic alterations in the joints (arthropathies). 

Pathogenesis. There is a primary hyperplasia of the con- 
nective tissue and neuroglia, which begins in the ganglia on the 
posterior root and in the pia about the roots and the posterior 
columns. 

Amyotrophic lateral sclerosis has the character of a descending 
degeneration. We have degeneration of the ganglion cells of the 
anterior horns and of the motor tracts of the cord. It is most 
marked in the cervical region. 

Pathogenesis. Amyotrophic lateral sclerosis is probably a 
primary degeneration of the ganglion cells. 



156 NOTES ON PATHOLOGY. 

Bulbar palsy. This is a primary degeneration of the motor 
ganglion cells in the medulla, affecting the nuclei of origin of the 
facial, hypoglossal, spinal accessory, and vagus nerves. 

Lateral sclerosis, or Spastic paraplegia. The primary nature 
of this is questioned. The pyramidal tracts (especially the 
lateral) are said to be involved, but the lesions found at autopsy 
vary. 

Disseminated, multiple, or insular sclerosis. This is a process 
usually affecting both cord and brain, and characterized by the 
formation of gray patches which vary in size from those barely 
visible to others 3 and 4 cm. in diameter. The patches are gener- 
ally distributed along the central cavities of the cerebro-spinal axis 
— in the brain, we find them in the wall of the lateral ventricles, in 
the caudate nucleus and optic thalamus ; in the cord, near the 
central canal. 

The degeneration is of slow development; the axis cylinder 
may remain intact long after the myelin has disappeared ; eventually 
it also degenerates, and is replaced, like the other structures, by 
neuroglia. The microscopic appearance is the same as in the 
systemic degenerations, i. e., we have an excess of neuroglia. 
Amyloid bodies are rare. 

The patches may become cystic from degeneration of the 
neuroglia. 

In all the degenerations two stages are recognizable — (a) the 
degeneration of the nerve substance, {b) the replacement by 
neuroglia. Both go on simultaneously, but in certain areas we 
find one more prominent than the other. 

Congenital Degenerations. — Syringo-myelia. In this dis- 
ease cavities of varying length surround the central canal of the 
cord, particularly in the posterior region of the upper part of the 
cord. It occurs early in life, and is the result either of a congenital 
insular sclerosis with cystic change or of a true gliomatous forma- 
tion, with softening of the tumor. 

Porencephalon. This is a condition in which through some 
disturbance, intra- uterine or early in life, a part of the brain degen- 
erates, and is replaced by fluid (vacuum dropsy). It is comparable 
to syringo-myelia. 

Circulatory Disturbances.— ^/z^/zia. The presence of 
blood in the dependent parts of the nervous system is not a sign 



CIRCULATORY DISTURBANCES. 157 

of active congestion. The existence of the latter can only be pre- 
dicated when we find the capillaries of the nerve structures filled 
with blood. Post-mortem congestion is generally limited to the 
membranes. The color of the gray matter when congested is 
peculiar : it is much darker than normal. The white matter has a 
punctated appearance, and may be the seat of minute hemorrhages. 

Edema is most marked in the subarachnoid space ; the nerve 
substance is soft and moist. In porencephalon we have a large 
accumulation of fluid in a depression of the brain — vacuum dropsy. 

Hydrocephalus is a collection of fluid in the ventricles of the 
brain ; the corresponding condition in the cord is known as hydro- 
myelia, or hydrorhachis. Hydrocephalus is generally due to a chronic 
inflammation of the ependyma, either simple or tuberculous. The 
ependyma is cloudy and granular, and to the finger conveys the 
sensation of a cat's tongue. There may be distinct tubercles. 

Hemorrhages are of two kinds, (a) extensive, and {b) punctated, 
or capillary. 

(a) Extensive hemorrhage. This is the ordinary lesion of apo- 
plexy and hemiplegia, and occurs from the branches of the middle 
cerebral artery piercing the anterior perforated space and going to 
the striate body, the optic thalamus, and the internal capsule. 
These arteries, as already stated, are subject to great pressure; they 
are, therefore, frequently the seat of sclerosis and miliary aneurysm. 
The hemorrhage may burst through the basal ganglia into the 
ventricles. 

(b) Punctated hemorrhages occur principally on the periphery 
of the brain, in the cortical portion, and are usually due to embol- 
ism or thrombosis. There is a tendency to the formation of a 
hemorrhagic infarct, but the latter is not well circumscribed. 
Embolic hemorrhages are most common in the motor area, the 
region of distribution of the sylvian artery. 

Thrombotic hemorrhage may occur anywhere in the brain. 

From the close aggregation of fibers in the internal capsule, a 
hemorrhage involving it, even if small, will lead to hemiplegia of 
the opposite side, or to hemianesthesia, if back far enough. As 
the fibers spread out in a fan-like fashion toward the cortex, a 
hemorrhage on the surface 0/ the brain usually produces a mono- 
plegia. 

Consequences of hemorrhage. The first effect is acute soften- 
ing, red or yellow. The softened tissue is converted into an 



158 NOTES ON PATHOLOGY. 

emulsion, the blood pigment being transformed into hemosiderin at 
the periphery, into hematoidin at the center of the area. Finally, 
both the pigment and the fatty detritus may be absorbed and be 
replaced by a cyst or a scar. Usually the cyst or scar contains 
evidences of pigmentation. 

Inflammation of the nerve centers resembles in its early 
stages the process of softening, in the later, that of sclerosis. In 
the acute stage we find the same changes as in softening, but in 
addition the evidences of inflammation — hyperemia, minute hemor- 
rhages, filling of the perivascular spaces, and cell-proliferation. 
The nerve tissue may break down and a true abscess be formed, 
which eventually is replaced by a scar or by a cyst. 

Suppurative inflammation is common in the brain {acute sup- 
purative encephalitis), and gives rise either to a single large or to 
many small abscesses. The former is usually due to extension from 
disease of the middle ear or the nasal cavities, but it may be pro- 
duced by the coalescence of several small abscesses. The small 
abscesses are generally embolic in origin, being secondary to ulcera- 
tive endocarditis, pneumonia, or other pyogenic processes. 

Suppurative myelitis is due either to extension of suppuration 
from the vertebrae or to septic emboli. 

With the naked eye it is often impossible to distinguish between 
inflammation and ordinary softening. Abscesses usually have a 
pyogenic membrane, while in softening there is a gradual decrease 
of the soft character toward the periphery. But there may be 
abscesses without a limiting membrane ; in such cases the discovery 
of pyogenic micro-organisms will alone aid us. 

In some of the inflammations of the nerve centers there is no 
breaking-down, but a tendency to proliferation of the neuroglia, 
i. e., to sclerosis. This is best seen in acute anterior poliomyelitis, 
or infantile palsy. This is an acute febrile disease of childhood, 
probably infectious in origin. In the early stages distinct evidences 
of inflammation are present, although cases rarely come to autopsy 
at this period. There is no tendency to suppuration, but there may 
be some softening. Later the neuroglia becomes hyperplastic and 
replaces the parenchyma. This disease is, therefore, a sclerosis of 
distinctly inflammatory origin. 

Other varieties of inflammation of the spinal cord are : 

Poliomyelitis — inflammation of the gray matter of the cord. 



SYPHILIS. 159 

Leukomyelitis — inflammation circumscribed to the white sub- 
stance. 

Transverse myelitis involves the entire cord transversely. 

Besides these we have diffuse, focal, and disseminated 
myelitis. 

Tuberculosis presents itself in two forms, (a) as a solitary 
tubercle or tumor (tyroma), and (b) as miliary tuberculosis. 

{a) The solitary tubercle may be small or as large as a hen's 
egg. It is irregular, and is found most often on the surface of the 
brain, involving the pia, but as a rule not the dura. Microscopi- 
cally, the periphery of the tubercle consists of granulation tissue 
containing bacilli, while the center is cheesy. 

(b) Miliary tuberculosis, or tuberculous meningitis. In this we 
find miliary tubercles scattered along the blood-vessels, together 
with a diffuse inflammation of the meninges. The base is most 
frequently affected. There is also a tuberculous inflammation in 
the walls of the vessels. 

Syphilis. — Gummata are common in the dura ; they are gen- 
erally smaller than tubercles and do not show the same tendency 
to cheesy necrosis. Besides gummata syphilis often produces the 
diffuse arteritis previously described. 

The differentiation from tuberculosis is at times difficult and 
can only be made by staining for the tubercle bacilli which, it should 
be remembered, however, are not easily found in tuberculosis of 
the brain. 

Syphilis, in addition to causing gummata and vessel changes 
is also the remote cause of certain degenerations, particularly post- 
erior sclerosis. 

Tumors of the brain. The location of brain tumors is as im- 
portant as their nature. Clinically, syphilitic and tuberculous 
growths are considered as tumors, and together with glioma, 
constitute 75 per-cent of all cerebral tumors. These three occur 
with about equal frequency, and are nearly always found at the 
periphery of the brain. Gliomas are not encapsulated and resemble 
the brain substance, but are usually somewhat darker, more trans- 
lucent, gelatinous, and frequently hemorrhagic. Sarcoma is most 
common in the meninges and is of the alveolar type, or it may be 
an endothelioma. Cancer is usually secondary; it may then be 



160 NOTES ON PATHOLOGY. 

found anywhere, perhaps most often in the white substance just 
below the gray matter. Primary cancer is rare ; when it does occur, 
it springs from the surface of the ventricles. 



PERIPHERAL NERVES. 

It is difficult to separate, in the peripheral nerves, degeneration 
from inflammation. By some all changes are considered degenera- 
tive, while others look upon the vascular changes as inflammatory. 
Taking the view that there are two different processes, we must 
admit that it is extremely difficult to say where certain of the 
changes belong. 

The most typical degeneration is seen after separation of the 
nerves from their trophic centers. Thus, if a spinal nerve be 
divided, the motor fibers degenerate in the distal part. In the case 
of the sensory nerves, the processes are more complex — some have 
their trophic centers in the ganglia on the posterior root, others at 
the periphery, in the sensory end-organs. 

Poisons may produce similar degenerations, although in some 
cases they cause inflammatory changes. 

Among poisons acting on the nerves, we have : 

1. Toxins of infectious diseases, (a) Beri-beri, which is an 
infectious disease, with neuritic and degenerative changes in the 
nerve fibers, these appearing as the characteristic symptoms of the 
disease before other phenomena manifest themselves, (b) Diph- 
theria. Post-diphtheritic paralysis is due to a degeneration of the 
nerves brought about by the toxins of the diphtheria bacillus, (c) 
Yellow fever, (d) Tuberculosis, (i) Syphilis. 

2. Non-bacterial poisons, as lead, and alcohol. 

Macroscopy. The nerves are swollen, and on section appear 
red and edematous. They are, however, rarely seen in the early 
stages. Microscopically \ the appearance is the same as in the white 
matter of the spinal cord — the myelin degenerates first, then the 
axis cylinder ; but the latter holds its own for a long time. 



THE MOUTH. 161 



CHAPTER XL 



DISEASES OF THE DIGESTIVE TRACT. 

THE MOUTH. 

Inflammation. Stomatitis. — We may look upon all 
forms of stomatitis as microbic in origin. The mouth is con- 
stantly the habitat of many kinds of bacteria which may cause in- 
flammation by becoming more virulent or, what is more probable, 
are enabled to start disease because the resistance of the mucous 
membrane is lowered. The lessened vitality may be produced by 
injuries (hot water or other irritants); even mercurial stomatitis is 
micro-organismal, the poison in its elimination producing a favorable 
soil in the mouth for the bacteria. 

In the common forms of stomatitis the organisms are not 
specific, but are the ordinary pyogenic bacteria found in the mouth. 

Varieties of stomatitis, (a) Catarrhal, which is either diffuse 
or follicular. In the latter the mucous follicles are especially 
affected and stand out as whitish points surrounded by a red areola. 

(J?) Ulcerative, or diphtheritic stomatitis, begins usually about 
the front teeth, and penetrates to the submucous tissue or even to 
the bone. It is characterized by a coagulation necrosis, whence the 
name diphtheritic, but is due to the ordinary organisms. 

(c) Gangrenous stomatitis, noma, or cancrum oris. This occurs 
when the vitality of the tissues is depressed to the lowest degree. 
It begins in the cheek, but may extend through and may even 
involve the entire side of the face. Although at times epidemic, it 
is probably not due to a specific micro-organism, but to the strep- 
tococcus, which renders the tissues a favorable soil for the sapro- 
phytic bacteria. 

Specific Inflammations.— (a) Aphthous stomatitis. This 
is probably due to a specific germ, perhaps the same one that 
causes foot-and-mouth disease, or murrain, in cattle. The disease 
is characterized by the formation of minute blebs — aphthce, which 
are at first clear, but later become opaque and whitish. The con- 
stitutional symptoms are slight ; the affection may be epidemic. 

11 



162 NOTES ON PATHOLOGY. 

(b) Mycotic stomatitis, or Thrush. The cause of this is a fungus 
standing between the yeasts and the moulds, probably somewhat 
nearer to the former. It is termed oidium albicans, or saccharomyces 
albicans. It grows between the epithelial cells and causes them to 
degenerate. Whitish patches are produced, consisting of degener- 
ated cells and masses of fungi. 

if) Syphilis. 

(d) Tuberculosis. 

(e) Actinomycosis. 

Malformations. — These are not rare and are due to failure 
of union of the palatal plates or the branchial arches. 

(a) Hare-lip results from non-union of the palatal plates ; the 
fissure may extend to the hard and soft palate ; at times, there is 
a complete division of the face into two parts. 

(b) Cleft tongue depends on a failure of closure of the branchial 
arches. 

Hypertrophies. — These are usually congenital and are, in 
reality, tumors, e.g., macroglossia, macrochilia, which are lymphan- 
giomata. 

Tumors. — (a) Carcinoma, (a) Squamous epithelioma occurs 
especially on the lower lip, between the median line and the angle 
of the mouth, and is usually superficial. ($) Glandular cancer — 
from the salivary glands. Cancer may occur in any part of the 
mucous membrane of the mouth. 

(b) Sarcoma develops generally from the gums, particularly 
the giant cell sarcoma (malignant epulis) which grows from the 
alveolar process. 

(c) Cysts, (a) Retention cysts of the mucous glands ; (/3) 
ranula. 

THE SALIVARY GLANDS. 

Inflammation. — (a) Mumps, or infectious parotitis. This is 
a true inflammation of the parotid gland, contagious and epidemic. 
There is no tendency to suppuration. The infection takes place 
through the duct of the gland. 

(b) Suppuration. The pyogenic organisms reach the salivary 
glands through the ducts or the lymphatics. Suppuration is com- 
mon in scarlet fever and diphtheria, and is usually due to the 
streptococcus. 



FAUCES AND PHARYNX. 163 

(c) Angina Ludovici — a peculiar suppurative inflammation of 
the submaxillary glands, at times epidemic. 

Tumors. — (a) Adenomatous cancers of glandular type. 

(b) Tubular epithelioma. This is a peculiar form of epithelioma, 
occurring in the salivary and mucous glands, in which the nests 
have a cylindrical shape, extending into the tissues and lymphatics, 
and resembling to a certain extent endothelioma. The diagnosis 
may be made by the presence of pearly bodies in the epithelioma. 
The tumor is usually non-metastatic, but spreads widely locally. 

(c) Mixed tumors are common in the parotid, and are combina- 
tions of fibroma, myxoma, and chondroma, and often sarcoma. 
They bear out Cohnheim's theory of tumors. 

FAUCES AND PHARYNX. 

Lymphatic tissue is very abundant in the pharynx and is dis- 
tributed in three groups, (a) the lingual tonsil, at the base of the 
tongue ; (b) the faucial tonsil, between the pillars of the fauces, and 
ordinarily referred to as the tonsil, and (c) the pharyngeal tonsil in 
the naso-pharynx. These three sets of tonsils form a lymphoid 
ring which guards the pharynx and prevents general infection. It 
has probably been developed as the result of frequent infections in 
early life. 

Inflammation. Pharyngitis. — {a) Catarrhal pharyngitis 
is diffuse or follicular. In the latter the glands are enlarged and 
discharge a creamy secretion. If this spreads over the surface an 
appearance resembling diphtheria is produced, but the opening of 
the follicles can usually be seen, and pressure forces out more of 
the secretion. 

(B) Herpetic pharyngitis is more common than is believed. It 
corresponds to herpes labialis and occurs most frequently in per- 
sons subject to herpes of the lips or prepuce. It has an acute 
onset, a continuous fever, and a sudden crisis, resembling in these 
respects croupous pneumonia. Vesicles form, particularly on the 
tonsils ; at first they are filled with a clear fluid, later this becomes 
opaque and whitish. On breaking a fibrinous membrane is pro- 
duced — a superficial diphtheritic membrane, differing from diphtheria 
in the absence of the Klebs-Lofrler bacillus. The cause is probably 
a specific micro-organism. 

(c) Pustular pharyngitis occurs in small-pox. 



164 NOTES ON PATHOLOGY. 

THE TONSILS. 

Of the three tonsils, the faucial or palatine tonsil is generally 
more markedly involved by disease than the other two. They are, 
however, also affected, although this fact is frequently overlooked. 

Inflammations. Tonsillitis, Amygdalitis. — (a) Ca- 
tarrhal tonsillitis. The tonsil participates in acute catarrhal in- 
flammations of the pharynx. 

(S) Follicular, or lacunar tonsillitis. The tonsillar crypts are 
filled with a yellowish-white secretion composed of broken-down 
epithelium. When this extends over the surface an appearance 
resembling diphtheria is produced. The patch is, however, easily 
removed, the openings of the follicles can be seen, and more secre- 
tion can be pressed out. 

(c) Herpetic tonsillitis. It is on the tonsils that herpes of the 
pharynx shows itself best. 

(d) Pustular tonsillitis is seen in small-pox. 

(e) Suppurative tonsillitis, abscess, or quinsy. The tonsils have 
a special tendency to suppurate, and, considering the number of 
micro-organisms always present in the crypts, the wonder is that 
suppuration is not even more common than it is. The abscess may 
begin in the tonsil or in the peri-tonsillar tissues ; it is usually due 
to the staphylococcus or streptococcus, at times to the pneumo- 
coccus. 

Chronic Inflammation of the Pharynx.— In the hyper- 
trophic stage the hyperplasia affects either the lymphoid or the 
mucous follicles, in both cases producing a granular appearance. 
When the first are affected we speak of granular pharyngitis, when 
the mucous follicles are involved, of follicular pharyngitis. 

Atrophy in time supervenes and gives rise to a smooth, shining 
membrane, with cicatricial markings and dilated veins. 

Chronic Tonsillitis.— a Hypertrophy of the tonsils." In 
many cases the hyperplasia involves all the elements ; at times the 
lymphoid tissue is especially affected, at times the connective tissue 
— in the former the enlargement is soft, in the latter hard. 

The lymphoid hyperplasia of the pharyngeal tonsil (" the 
adenoid growths of the naso-pharynx ") interferes with nasal breath- 
ing, and is of great clinical importance — it seems to retard the 
physical and mental development of the children affected. 



THE TONSILS. 165 

Specific Inflammations. — (a) Diphtheria. — This is 
due to the Klebs-Loffler bacillus, a facultative, aerobic, non-motile 
bacillus, not liquefying gelatin, about the length of the tubercle 
bacillus, but much broader. Its characteristics are irregularity in 
shape, and variation in staining. It grows on all media, but best on 
Loffler's blood serum mixture [Blood serum j, bouillon containing 1 
per-cent. of glucose, 1), and on coagulated white of egg. 

The diagnosis may sometimes be made by finding a pure cul- 
ture of the bacillus in the deeper parts of the membrane, usually, 
however, it is necessary to resort to cultivation. A small cube of 
coagulated white of egg is placed in a test-tube with a little water, 
and sterilized by boiling. A bit of membrane is removed and 
rubbed on the surface of the egg, and the tube then placed into the 
incubator, at 37°C. In from 14 to 24 hours a characteristic growth 
appears in the form of circular white colonies with a convex surface. 
A cover-glass preparation should be made; but the appearance 
of the colonies is quite diagnostic. 

The streptococcus pyogenes often causes false membrane for- 
mation, but its growth in culture media is different and much slower, 
colonies rarely appearing under 48 hours. The angina produced 
by it is also milder. 

Mixed infection is common in diphtheria. 

The various phenomena of diphtheria are due to two poisons 
elaborated by the bacillus, a nuclein and a nucleo-albumin. The 
nucleo-albumin is destroyed by proteolytic ferments, the nuclein 
is not. 

The nucleo-albumin gives rise to the acute manifestations of 
diphtheria, the nuclein to the later symptoms, as the cachexia. 

Immunity may be induced in animals (a) by feeding them with 
cultures of the bacillus, (b) by employing bacilli grown under un- 
favorable conditions, e. g., at a high temperature or in culture 
media containing iodin trichlorid, (c) by treating them after the 
method of intensification, i. e., injecting first attenuated bacteria and 
then gradually using stronger and stronger cultures. 

The blood serum of animals made immune contains an anti- 
toxin, which when the serum is injected into other susceptible 
animals, renders them also immune. 

The pseudo-diphtheria bacillus is now considered an attenuated 
form of the true diphtheria bacillus. It may be normally present 
in the mouth, and under certain conditions may produce a mild 



1 66 NOTES ON PATHOLOGY. 

inflammation, at times pseudo-membranous. It is non-pathogenic 
to lower animals. 

Diphtheroid inflammations can be produced in the pharynx, 
larynx, bowel, etc., by other micro-organisms than the Klebs-Loffler 
bacillus, especially by the streptococcus. Anatomically, the mem- 
brane is indistinguishable from that of true diphtheria, but the 
disease is milder in type. Streptococcus membranes may occur in 
any infectious disease, particularly in scarlet fever, measles, and 
typhoid fever. At times both the streptococcus and the bacillus of 
diphtheria are present together. 

Syphilis. — The commonest lesion is the mucous patch ; 
chancre may occur in the pharynx. The gumma is quite frequent 
and leads to destructive changes, especially in the hard and soft 
palate. The healing of the ulcers gives rise to stellate scars. 

Tuberculosis is not rare in the palate, but is often over- 
looked. Usually it is a secondary lesion. The tonsil is by some 
considered a frequent primary seat, but more probably is infected 
secondarily from the lung. Lupus of the face may extend to the 
pharynx. 

THE ESOPHAGUS. 

Malformations. — (a) Congenital diverticula. These are lat- 
eral, and are most common in the upper part of the esophagus. 
They are due to faulty union of the branchial arches. 

(J?) Acquired diverticula or pouches. These are not true mal- 
formations, but are due to pathologic changes, the causes of which 
are not always discoverable. They occur on the anterior and pos- 
terior wall of the gullet. The posterior diverticida are the result of 
ulceration produced by a foreign body ; the anterior are due to rup- 
ture of a bronchial gland into the esophagus (this may occur with- 
out symptoms) and the formation of adhesions which in contracting 
produce a diverticulum. 

Stricture. — Stricture is prone to occur at two points in the 
esophagus — opposite the cricoid cartilage and the bifurcation of 
the trachea. At these points the cartilages are complete rings and 
produce to all intents and purposes a normal stricture. 

Causes of stricture, (a) Disease of the walls of the esophagus. 
(a) Spasmodic stricture — in hysteria ; (0) cicatricial stricture — due 
to the healing of lesions produced by corrosive poisons, hot water, 



THE STOMACH. 167 

etc.; (y) cancerous stricture. The last is the most common, and oc- 
curs at the two points of normal coarctation, a fact to some extent 
supporting the mechanical theory of tumors. The cancer is usually 
primary ; it is squamous in type, and very destructive. 

(b) The presence of a foreign body. 

(c) Pressure from without, as by an aneurysm (most frequent) ; 
or by tumors of the neck or mediastinum. 

Rupture Of the Esophagus. — This may be due to cancer, 
to perforation by an aneurysm, to ulceration of a diverticulum, or 
it may occur spontaneously from violent retching and vomiting. In 
the last, the rent begins at the bifurcation of the trachea, as this was 
the case in a recent instance. 

THE STOMACH. 

The most fixed portion of the stomach is the cardiac orifice, 
which is situated in front and to the left of the last dorsal vertebra. 
The pylorus and the greater curvature are quite movable ; the lesser 
curvature is relatively more fixed. 

Size and weight. The stomach is 20-30 cm. long, 10-12 cm. 
wide, and weighs 130-140 grams. 

The wall consists of four coats, (a) the serous, (/;) the muscular, 
(c) the submucous, and (d) the mucous. The mucous membrane 
is thrown into a series of longitudinal folds, or rugae, which, how- 
ever, are not seen when the organ is distended. The epithelial 
lining of the stomach consists of tall, columnar cells, which secrete 
mucus. Two kinds of glands are found in the stomach — the 
pyloric and the cardiac. 

The pyloric consist of a long duct with two or three out- 
growths constituting the body of the glands ; the cardiac have a 
short duct which communicates with three or four secreting sacs. 
The epithelium of the glands is cuboidal, and is of two kinds (a) the 
central, chief, or peptic cells, and (J?) the parietal, placed between 
the central cells and the basement membrane, and staining deeply. 
The central cells are the most important ; they secrete the pepsin, 
while the parietal, which are found only in the cardiac glands, 
elaborate the HC1. 

Lymphoid tissue is abundant in the stomach, and at the pylorus 
forms a distinct ring. The nodules are well circumscribed but have 
no capsule, and are often mistaken for inflammatory round cell infil- 
tration. 



1 68 NOTES ON PATHOLOGY. 

Physiology of Digestion.— Digestion, not alone in the 
stomach, but anywhere, depends largely upon the action of fer- 
ments. Ferments are substances which are capable of starting up 
chemical changes in certain other substances with which they are 
brought in contact. They are of two kinds : organic, or soluble 
substances, and organized, as bacteria and yeasts. Fermentation 
seems to be a function of protoplasm ; bacteria, which are but cells, 
have the power in a marked degree. Classified according to their 
properties, we have the following ferments : 

(a) Sugar-producing, or diastatic ferments. These are found 
in saliva, pancreatic and intestinal juice, blood, urine, bile, milk, 
fluids from dead tissues, and solutions of albuminous substances. 

(b) Proteolytic ferments. These act upon albuminous sub- 
stances, and are found in the stomach (pepsin), in the pancreatic 
juice (trypsin), in the intestinal juice, and in the urine. The 
products of albuminous fermentation (albumoses and peptones) 
may be actively poisonous when introduced into the circulation. 
In health they do not enter the blood as peptones and albumoses, 
but are altered in the walls of the digestive tract. Fermen- 
tation changes of albumins may take place anywhere in the body 
— under the influence of cells or micro-organisms. Many disease 
poisons are produced in this way. 

(c) Fat-splitting agents. These are probably not true ferments ; 
they are found in the stomach and pancreas. 

(d) Milk-curdling ferment, rennet, or rennin. This exists in 
the stomach, pancreas, and urine. 

In the process of digestion proteids are transformed into albu- 
moses and peptones which, however, are not absorbed as such, but 
are converted into forms of albumin by the epithelial cells, leuko- 
cytes, and lymphoid corpuscles of the walls of the stomach and 
intestine. In the tissues they are further changed into the con- 
stituents proper to these, as, e. g., into globulins or myosin. When 
injected into the circulation or produced in the body in certain forms 
of chronic suppuration, peptones give rise to toxic symptoms ; they 
act as narcotic poisons, produce fever, and diminish the alkalinity 
and coagulability of the blood. In certain acute infectious diseases, 
in which there is an arrest of digestion, some of the symptoms may 
be due to the absorption of such products. 

The gastric juice. The active agents of the gastric juice are 
pepsin and hydrochloric acid. The former is practically always 



THE STOMACH. 169 

furnished in sufficient quantity; the latter may be increased or 
decreased. The HC1 is essential; just enough is normally present 
to bind the bases and to leave a little free. The normal quantity 
of free HC1 is so small that the chemical reaction is feeble, but 
distinct. 

Hyperacidity. The effects of this are (a) rapid digestion of 
the proteids, which is not an advantage ; it may cause disturbances ; 
(b) injury to the mucous membrane — at times leading to the forma- 
tion of ulcers ; (c) the development of yeast fungi which grow well 
in an acid medium — they act upon the carbohydrates and produce 
H, C0 2 , CH 4 ; (d) an arrest of the salivary digestion which normally 
continues for a short time in the stomach. Hyperacidity is rare. 

Subacidity. Causes: (a) Lesions of the mucous membrane; 
(b) nervous disturbances; (c) accumulation and retention of food 
and of the products of digestion. 

The effects of subacidity are the following : (a) Proteids, all 
or in part, pass into the intestines undigested and set up diarrhea. 
(b) Bacteria develop, particularly those producing lactic, butyric, 
and acetic acids. These give rise to an induced hyperacidity, which 
in turn favors the development of the yeasts. The amount of lactic 
acid is insufficient to digest the proteids, although it is capable, in a 
slight degree, of taking the place of the HC1. The presence of the 
organic acids is the cause of " acid dyspepsia." (c) Putrefactive 
changes develop, and may lead to the production of ptomains, the 
absorption of which gives rise to a toxemia. Ordinarily, ptomains 
and other poisonous substances formed during digestion are de- 
stroyed in the liver, but when that organ is disturbed, the poisons 
are absorbed and cause the nervous symptoms accompanying dys- 
pepsia, (d) The absence of HC1 favors infection with pathogenic 
bacteria. The majority of noxious micro-organisms are prevented 
from entering the intestines by the antiseptic action of the gastric 
juice. This is especially true of cholera. Experimentally, it is 
impossible to produce that disease in lower animals on account of 
the acidity of the gastric juice. But if the acid is neutralized with 
sodium carbonate, and if, at the same time, peristalsis is checked 
with opium, cholera can be given to the lower animals. 

The muscular coat is also an important factor in digestion. 
When weakened the organ becomes dilated. Causes of dilatation : 
(a) Fermentation of the food, leading to distention of the stomach 
with gas. (b) Obstruction at the pylorus, (c) Nervous disturbances. 



170 NOTES ON PATHOLOGY. 

Given any one of these, the others soon supervene, all acting" 
together in a " vicious circle." 

Post-mortem Lesions of the Stomach. — These may 
simulate true lesions or conceal disease previously existing. 

(a) Post-mortem digestion of the stomach wall. This may be dis- 
tinguished from ante-mortem lesions (a) by being limited to the 
posterior wall of the stomach, in the region of the fundus — ante- 
mortem lesions being most marked toward the pylorus ; (b) by 
extending only as far as the upper level of the gastric contents. 

Two forms of digestion are described, the white and the brown. 
In the former the mucous membrane is converted into a whitish, 
gelatinous material, which may easily be mistaken for mucus. 
Mucus, however, is more readily washed off. In the latter, the 
same changes take place, but owing to the presence of blood pig- 
ment, the color is brownish. Digestion may proceed to perfora- 
tion of the stomach wall. Putrefactive changes may occur in the 
stomach after death. The parts are greenish in color and emphy- 
sematous. 

(o) Hypostasis. The blood after death gravitates toward the 
dependent parts of the stomach, particularly the posterior wall 
toward the fundus. Post-mortem digestion may affect the walls of 
the distended veins and cause the hemoglobin to pass out, giving 
rise to an appearance of hemorrhages. 

Disturbances Of Circulation.— I . Active hyperemia results 
chiefly from the action of irritants, and is best marked toward the 
pyloric end, on the crests of the mucous membrane. 

2. Passive congestion is due to liver or heart disease, and is also 
seen most prominently toward the pylorus. 

Both active and passive hyperemia may give rise to petechial 
hemorrhages which, unlike the post-mortem petechiae, are distribu- 
ted anywhere in the stomach, but especially in the neighborhood of 
the pylorus, and have no connection with the large veins. In 
passive congestion we often find minute dark or slate-colored spots, 
due to small hemorrhages. 

3. Hemorrhage. This may result (a) from the entrance of 
blood into the stomach from neighboring parts — as from rupture of 
an aortic aneurysm ; (b) from disease of the vessel walls of the 
stomach, as in yellow fever, the purpuric diseases, cancer, tubercu- 
losis, and simple ulcer. The vomited blood is generally partially 



THE STOMACH. 171 

digested, is dark in color, and resembles " coffee grounds," espe- 
cially if the hemorrhage has been slow. When the hemorrhage 
is sudden and rapid, the blood is clotted. 

Inflammation. — {a) Catarrhal gastritis. The mucous mem- 
brane is swollen, especially toward the pylorus, the veins are in- 
jected, and there is a diffuse redness ; the surface is covered 
with blood-stained mucus, and may show petechial hemorrhages. 
Swelling of the mucous membrane is not easily discerned ; it may 
be recognized by contrasting the gastric mucous membrane with 
that of the esophagus. Normally, there is a sharp line of separa- 
tion at the cardia, the esophageal mucosa being thicker; in 
catarrhal gastritis this relation may be reversed. 

Microscopically \ we find filling of the capillaries, and cloudy 
swelling and desquamation of the central cells of the gastric tubules. 
The glands are distended by the accumulation of cells and mucus. 

Causes. These are innumerable, and are either irritants intro- 
duced from without or irritants produced in the stomach. 

(b) Diphtheritic gastritis. This is a coagulation necrosis which 
is usually most marked on the rugae, appearing in the form of 
grayish- white lines. The crests may be alone affected ; at times the 
process is more extensive, and we may then have a complete cast 
of the stomach. 

Causes. The coagulation necrosis is generally due to micro- 
organisms — in rare cases to the diphtheria bacillus, but more com- 
monly it is seen in other infections, as scarlet fever, typhoid fever, 
pyemia, etc. It may be produced by corrosive poisons. 

(c) Suppurative gastritis, (a) Submucous abscess. This dis- 
sects along the coats of the stomach, lifting up the mucous mem- 
brane, and finally discharges into the stomach through numerous 
openings like a carbuncle. A large ulcer is left which, if death 
does not take place, heals with extensive scar formation. 

Causes. These are always micro-organismal, but the point ot 
entrance is not in every case discoverable. (1) They are most 
common in drunkards— {idiopathic abscess of drunkards}) (2) Pyemia 
produces multiple abscesses. (3) Abscesses may occur about 
tumors and ulcers. 

(/3) Follicular suppurative gastritis. Small abscesses are formed 
in the lymphoid nodes of the mucous membrane. Causes. Small- 
pox, typhoid fever ; tartar emetic when introduced through another 
channel than the stomach. 



172 NOTES ON PATHOLOGY. 

Chronic Inflammation. — (a) Chronic catarrhal gastritis. 
In this we have a uniform thickening of the mucous membrane, 
generally most evident in the pyloric region. The mucosa is con- 
gested, the veins are prominent, and pigmentation is marked, either 
in the form of minute dark points or as a diffuse slate-colored 
deposit. The surface is covered with a thick tenacious mucus. 

(b) Chro?iic productive gastritis. This is characterized by a 
marked hyperplasia of the glands and the connective tissue of 
the mucous membrane. To a certain extent this is present in all 
chronic inflammations, but in the form under discussion it becomes 
a very prominent feature and gives rise to localized swellings, par- 
ticularly of the rugae. Normally, the latter can be made to 
disappear, but this is not possible in productive gastritis. Micro- 
scopically, we find the glands elongated, tortuous, and possessing 
more sacs, while between them we find an embryonal connective 
tissue. On account of the glandular hyperplasia it is not always 
easy to distinguish this condition from adenoma. By occlusion 
of the gland ducts minute cysts are formed. 

In some instances the hyperplasia is so great as to give rise to 
circumscribed projections of the connective tissue covered by 
epithelium — gastritis poly posa. Cysts are very common in this form. 

Atrophic gastritis. The hyperplasia of the mucous membrane 
is often followed by atrophy, brought about by the contraction of 
the connective tissue. The mucous membrane becomes smooth 
and resembles a serous membrane. The glands are either entirely 
removed or remain as mere shallow depressions. There may be 
cicatricial markings. 

In chronic catarrhs, especially in cases where there is distention 
by gases, the muscular coat is apt to take part in the hyperplasia. 
This occurs especially toward and at the pylorus and may give rise 
to obstruction. It is termed fibroid thickening of the pylorus by 
clinicians. 

In chronic inflammations congestions are very frequent; these 
or the cellular proliberation may interfere with the nutrition of the 
stomach wall and lead to ulceration from digestion. 

Causes of chronic inflammation, (a) Venous stasis, produced 
by cirrhosis of the liver, by pressure of tumors on the return circu- 
lation, or by heart-disease, (b) Bright's disease — probably the 
inflammation depends on an attempt by the gastric mucous mem- 
brane to eliminate excrementitious substances, (c) Ingestion of 



THE STOMACH. 173 

improper food, e. g., alcohol, (d) Tumors. Chronic inflammation 
is common about tumors, and is also produced by the dyspeptic 
conditions associated with their presence. 

Infectious Diseases. — (a) Acute catarrhal gastritis is seen 
in nearly all infectious fevers and probably results from the action 
of the imperfectly digested food, digestion being arrested. In 
yellow fever the stomach may be the seat of the specific organism 
causing the disease. There is generally a catarrhal gastritis in 
cholera. 

(fr) Chronic infections, (a) Tuberculosis. This is rare : it may 
be miliary, but usually is in the form of a tuberculous ulcer situated 
toward the pylorus. (|3) Syphilis is very rare. 

Tumors. — It is difficult to draw a sharp line of distinction 
between the hyperplasia of chronic inflammation and adenoma. 

(a) True adenoma occurs especially toward the pylorus in the 
shape of fungoid masses. Histologically, it is a tubular adenoma 
with cylindrical epithelium. It may infiltrate and then is termed 
adenoma destruens. 

(b) Carcinoma is common, and may be glandular or cylindrical ; 
at the cardia we may have a squamous cancer coming from the 
esophagus. The most frequent seats are the pylorus, the cardia, 
the lesser curvature, and the posterior wall. The cancer may be 
scirrhous, medullary, or, occasionally, colloid. The last occurs either 
in the form of nodes or, more commonly, as an extensive diffuse 
growth. 

Cancer of the stomach has a marked tendency to give meta- 
stasis, particularly to the liver, but it may go anywhere. To the 
bones metastasis is rarer than in the case of primary mammary cancer. 

Effects of cancer. Cancer of the pylorus causes obstruction, 
and the concomitant dyspeptic disturbances. Any cancer may give 
rise to ulceration, to hemorrhage, or to perforation into the peri- 
toneal cavity. The last may be prevented by adhesions. 

Free H CI is greatly diminished or entirely absent in carcinoma. 

Degenerative Processes. — (a) Fatty degeneration and atro- 
phy of the epithelium and glandular structure occurs in marasmus, 
in inanition, in hysteria from a refusal of food, in phosphorus 
poisoning, in leukemia, and in progressive pernicious anemia. In 
regard to the last two, the anemias, the question arises whether the 
fatty degeneration is primary or secondary. The weight of evidence 
is in favor of considering it secondary. 



174 NOTES ON PATHOLOGY. 

(J?) Gastric, peptic, simple, or round ulcer. This is due to diges- 
tion of a portion of the stomach wall, the resistance of which has 
been weakened by some degenerative process. The ulcer may be 
superficial or deep ; it may even extend through all the coats. It is 
usually round, " punched out," or funnel-shaped, becoming narrower 
toward the peritoneal coat, and has smooth edges. Generally there 
is but one ulcer, at times several are found. 

As a rule, the borders are pale and show no inflammatory 
processes, an evidence that the ulcer is due to digestion and not to 
inflammation. If, however, it has existed for a long time, micro- 
organismal infection may take place, the ulcer then becoming 
inflamed ; connective tissue forms which may go on to contraction. 
Healing may thus take place, a stellate scar with a puckered 
center marking the site of the ulcer. 

In some cases instead of being crater-like, the ulcer becomes 
undermined by the digestive processes, a condition most apt to 
occur when the ulcer has formed adhesions to neighboring parts, 
as the pancreas, liver, spleen, or abdominal wall. The digestive 
process may travel along the adhesions producing extensive under- 
mining. 

Seats. The most frequent seat is on the lesser curvature 
toward the posterior wall. 

Accidents in the course of ulcer, {a) Hemorrhage, (b) Per- 
foration, (c) Adhesion to neighboring organs with abscess in these 
organs. 

Pathogenesis. The ulcer is due to the action of the gastric 
juice on a weakened part of the stomach wall. 

Causes lessening the resistance of the mucous membrane. 

I. Circidatory disturbances. 

(a) Embolism and thrombosis. These give rise to a hemorrhagic 
infarct or an area of coagulation necrosis upon which tfye gastric 
juice then acts. This can be demonstrated experimentally. 

(b) Petechial hemorrhages, as in catarrhal inflammations. They 
give rise to a partial necrosis of the mucous membrane. 

(c) Obliterating endarteritis. This usually acts by inducing 
thrombosis. 

{d) Chronic venous stasis. 

(e) Spastic contraction of the vessels, causing circulatory dis- 
turbances in localized areas. It may be brought about in one of 
two ways : (i) by an irregular contraction of the muscular coat 



THE INTESTINES. 175 

occluding certain vessels, (2) by a neurotonic spasm of the vessels. 
The latter is quite frequent in grave hysteria — there is an ischemia 
of the gastric mucous membrane analogous to that of the surface 
of the body. 

II. Inflammation of the mucous membrane. 

III. Bacterial infection of the mucous membrane. 

IV. Lessened alkalinity of the blood. 

Apart from the distinct peptic ulcers described above, we may 
have at the pylorus superficial abrasions which, although fre- 
quently overlooked, are important, inasmuch as they cause a con- 
dition clinically known as irritable pylorus, a spastic contraction, with 
secondary hyperplasia of the muscular coat and the connective 
tissue. The closure of the pylorus gives rise to dyspeptic symp- 
toms from the retention of the food, and also to many reflex 
disturbances, comparable to those produced by fissure of the anus 
or laceration of the cervix uteri. 

THE INTESTINES. 

Automy. The coats are the same as those of the stomach — a 
loose mucous membrane, a submucous, two muscular, and a serous 
coat. The entire intestinal tract, except the lower third of the 
rectum, is lined by columnar epithelium. Two kinds of glands are 
found — racemose glands (Brunner's glands), confined to the duo- 
denum, and simple tubular glands (crypts of Lieberkuhn). 
Throughout the intestines we find lymphoid follicles possessing a 
distinct wall. In the lower part of the small intestine they are 
gathered in groups to form 10 to 15 large, oval plaques (Peyer's 
patches, or agminated glands), placed opposite the attachment of the 
mesentery. The villi are covered by columnar epithelium ; they 
are chiefly concerned in absorption. 

Functions. In the intestines the changes begun in the mouth 
and stomach are continued. Trypsin, the powerful proteolytic 
ferment of the pancreatic juice, completes the digestion of the 
proteids ; another ferment acts on the carbohydrates, and another 
breaks up the fats and assists in their emulsification. The bile also 
contributes to the formation of the fat emulsion, acts on the 
mucous membrane in a way to favor the absorption of the fats, and 
is the natural antiseptic of the intestines. 

The reaction of the intestinal juice is alkaline, hence putrefac- 
tive changes readily take place, especially in the large intestine, 



176 NOTES ON PATHOLOGY. 

where the alkalinity is well marked. In the upper part of the 
small intestines the reaction of the juice is also alkaline, but the 
contents, especially in their interior, are acid. For this reason pu- 
trefaction is less apt to occur. 

Composition of the feces, (a) Undigested food. This may, in 
a small part, be digestible substances that have escaped digestion ; 
the greater part consists of undigestible material, such as cellulose, 
nuclein, chlorophyl, and salts, (b) Excretory products of the in- 
testinal tract. A large part of the secretion is reabsorbed. 

Diseases. Malpositions.— (a) Hernia. This is a protru- 
sion of any organ outside of the cavity in which it belongs. The 
word is, however, generally applied to a protrusion of the intes- 
tines outside of the peritoneal cavity. 

Varieties of intestinal hernia, {a) Internal hernia. One which 
pushes out of the peritoneal cavity without appearing externally, 
as diaphragmatic hernia. The term is also applied, improperly, 
however, to a loop of intestine caught beneath a band of ad- 
hesion. 

(b) External hernia. One appearing beneath the surface of the 
body. 

In pushing itself out of the abdominal cavity, the bowel carries 
a part of the peritoneum with it, which together with the muscles, 
subcutaneous tissue, fascia, and skin, constitutes the covering of the 
hernia. The peritoneal covering is termed the sac of the hernia, 
and is divided by surgeons into the body — the part containing the 
intestine or omentum, the neck — the constricted portion, and the 
mouth — the opening into the peritoneal cavity. 

Hernias are also classified into {a) congenital, and (b) acquired. 

{a) Congenital hernia. One which is present at birth. It 
occurs wherever the abdominal wall is normally deficient — as at the 
umbilicus and the inguinal ring, but it may also take place at any 
point where there is a defect in the abdominal wall. 

(b) Acquired hernia. One developed in after-life; it usually 
occurs in the same places where congenital hernia is found. 

Classifying hernias as to position, we have as the most im- 
portant : 

{a) Inguinal hernia — one occurring at the inguinal ring, (a) 
Oblique — a hernia traversing the inguinal canal following the track 
of the testicle. When congenital, the hernia occupies the same 



THE INTESTINES. 177 

cavity as the testicle ; when acquired, it lies outside of the tunica 
vaginalis. (|3) Direct — one breaking through the abdominal wall at 
the external ring. 

(6) Femoral, or crural hernia. This follows the sheath of the 
femoral vessels and lies to the inner side of the deep epigastric 
artery. It is common in women. 

(c) Umbilical hernia is usually congenital, sometimes acquired. 

(d) Retroperitoneal hernia. One in which the bowel, usually 
the duodenum or jejunum, pushes itself back of the posterior layer 
of the peritoneum. 

Contents of hernias. In the common forms, femoral and inguinal 
hernia, we find the lower portion of the small intestine, sometimes 
the sigmoid flexure, particularly on the left side. In rarer cases the 
colon, the duodenum, or the jejunum, may form the hernial con- 
tents. The omentum may be present in the sac, either with the 
bowel or, rarely, alone. 

Anomalies of contents, (a) The omentum, when present alone 
or with the intestine, is apt to become hyperplastic ; it may origi- 
nally have been only an epiploic appendage, (b) The part of the 
bowel forming the hernial contents may be a diverticulum, either 
Meckel's or a special one formed by the hernia itself in the follow- 
ing way : A large epiploic appendage becomes the contents of a 
hernia ; it forms adhesions to the sac, through which traction is 
exerted on the bowel causing a portion of the wall of the latter to 
come down and enter the hernial pouch. 

Causes of hernia. 1. Exciting — great efforts increasing the 
intra-abdominal pressure. 

2. Predisposing, (a) A congenital weakness of the abdominal 
wall, (b) Repeated pregnancies, (c) Operations — laparotomy, (d) 
An abnormally long mesentery rendering the intestine more mov- 
able. 

Changes in the hernial sac. Inflammatory changes are com- 
mon, but as a rule are slight, leading only to adhesions between 
the sac and the surrounding tissues or between the sac and the 
bowel. 

The intestine may slip back and leave the empty sac, the neck 
of which may become obliterated ; the sac then remains as a simple 
cyst. In some cases it disappears entirely through the formation 
of adhesions. When the bowel has becomes adherent to the sac 
the hernia is irreducible, a reducible hernia being one which can be 

12 



178 NOTES ON PATHOLOGY. 

returned into the abdominal cavity. In reducing a hernia both 
bowel and sac may be reduced, or the former only, if the sac has 
formed adhesions to the surrounding structures. 

Changes in the hernial contents. These are principally obstruc- 
tion of which two degrees are described, (a) Incarceration. This 
is due to an accumulation of feces in the intestine, and is as a rule 
readily overcome. (B) Strangulation. This is obstruction in which 
the circulation of the wall of the gut is interfered with, in conse- 
quence of which disturbances of nutrition result, which terminate 
in necrosis. The 'circulation in a hernia is at all times precarious, 
and venous engorgement is easily produced. If the obstruction is 
slight, inflammatory changes set in and give rise to adhesions ; 
severe obstruction leads to gangrene. 

Dilatation and Diverticula, (a) Dilatation may occur 
above strictures, (fr) It may be due to fecal accumulations. These 
in turn are dependent either upon habitual constipation or upon in- 
testinal dyspepsia, (c) There may be a congenital defect, either in 
the muscular wall or in the innervation, circumscribed to a part of 
the bowel or involving the entire colon. 

/;/ false diverticula only a part of the intestinal wall is com- 
prised in the dilatation. There is primarily a defective condition of 
the muscular coat, from fatty degeneration or other causes, which 
permits the mucous membrane to slip through and to bulge the 
serous coat outward. In time the mucous membrane may atrophy, 
leaving only the peritoneum. These diverticula occur near the 
attachment of the mesentery. 

Meckel's diverticulum is the remnant of the omphalo-mesenteric 
duct, the embryonic communication between the intestine and the 
umbilical vesicle. It is variable in size, and is usually attached 
about one meter above the ileo-cecal valve. 

Volvulus. — This is a twisting of the intestinal coils upon 
themselves. The condition is rare in a normal peritoneal cavity ; 
as a rule there are bands of adhesions through which the bowel 
passes. The displacement interferes with the circulation and may 
lead to sloughing. 

Intussusception, or Invagination is a condition in 
which one part of the bowel is driven into the part beyond. It occurs 
most frequently at the ileo-cecal valve, the valve and ileum being 



THE INTESTINES. 179 

invaginated into the colon. We might, indeed, speak of the nor- 
mal position of the valve as one of intussusception. 

The condition is most common in children ; it gives rise to cir- 
culatory disturbances which may lead to gangrene and sloughing of 
the invaginated portion of the bowel, the case eventually terminat- 
ing in recovery in this way. Intussusception is frequently pro- 
duced during the death agony or immediately after death. It may 
be distinguished from that occurring under other circumstances by 
the absence of the signs of inflammation. 

Inflammation Of the Intestines. — (a) Catarrhal inflam- 
mation. This is due to irritants coming from the stomach or to irri- 
tants generated within the intestines. The former are represented 
by products of imperfect digestion or by noxious substances intro- 
duced from the mouth, as the saline purgatives. In the majority of 
instances an important part is played by the poisons elaborated by 
bacteria. 

Macroscopy. The mucous membrane is soft, swollen, ede- 
matous, and covered with a slimy mucus or a fluid resembling pus. 
The discharges may be very liquid, and when the mucus and puru- 
lent matter are suspended in the fluid, the appearance resembles 
that of " meal-soup." In ordinary cases the redness disappears after 
death, except perhaps in a few coils that may have found their way 
into the pelvic cavity. In severe inflammations there may be a 
diffuse redness, from capillary injection, and an arborescent appear- 
ance from the filling of the small veins. 

Follicular catarrhal inflammation is really a complication of the 
diffuse. If the follicles are prominently involved they present one 
of two appearances : in the early stages they stand out as minute 
red points ; in the later stages, when they are apt to be most promi- 
nent, they are light in color from anemia, due to the compression of 
the vessels by the excessive cellular proliferation. 

Superficial ulcers are common in acute inflammations, particu- 
larly on the valvulae conniventes and the ileo-cecal valve. 

Peyer's patches may be involved in follicular inflammation, but 
at times they escape entirely, even in typhoid fever. When affected 
in ordinary catarrhal inflammation they are prominent and have 
a smooth surface, differing in this respect from typhoid fever. 

Ulcers occurring in follicular catarrh affect the lymphoid fol- 
licles and are deeper and somewhat undermined. They occur 
especially in subacute and chronic inflammations. 



1S0 NOTES ON PATHOLOGY. 

{b) Purulent enteritis. The suppuration is limited to the sub- 
mucous tissue, and is the result of extension of ulceration in the 
mucous membrane or of embolism in pyemia. 

Special Forms of Inflammation. — id) Inflammation of 
the duodenum. This is readily diagnosed on account of the presence 
of hepatic disturbances. The inflammation extends up the bile duct 
and may lead to obstruction. 

(b) Inflammation of the cecum and appendix. Typhlitis or, 
because most frequent in the appendix, appe?idicitis. The following 
conditions predispose to inflammation of the appendix, (i) The 
circulation in the appendix is precarious. Often there is no mesen- 
tery, the blood coming from the cecum — any obstruction at the 
base of the appendix will thus obstruct the circulation. (2) Being 
a closed sac, bacteria, especially the pyogenic forms, find a favorable 
nidus for growth in the appendix. (3) The same condition permits 
of the accumulation of foreign matter which acts as an irritant. 
(4) In many cases the appendix is bound down by adhesions or is 
misplaced, not infrequently presenting a condition bordering on 
volvulus. 

In rare cases the inflammation is circumscribed to the cecum. 
In typhlitis and appendicitis the inflammatory process usually 
extends through all the coats, inducing a local or general peri- 
tonitis — in the local form abscesses are found about the cecum or 
the appendix. Gangrenous changes, with sloughing of the appen- 
dix, may at times occur. 

A large number of bacteria are found in these inflammations ; 
principally concerned are the pyogenic organisms and the bacillus 
coli communis, which may be the only one present in perityphlitic 
abscesses. 

The immediate starting-point of appendicitis is a concrement 
that has found its way into the appendix from the intestines — usu- 
ally it is fecal matter containing a large amount of lime salts. In 
many cases the nucleus is probably a foreign body, as a small seed. 
That this is not discovered in the majority of instances is probably 
due to the fact that the body has undergone calcareous change and 
has become unrecognizable. 

Causes of Appendicitis. The following list is based on a re- 
view of 1 1 2 cases — (a) Fecal concretions (24) ; (b) foreign bodies 
(4); (c) tuberculosis (20); (d) diphtheritic inflammation (5); (e) 
typhoid fever (4) ; (/) puerperal abscess (3) ; ( g ) carcinoma (3) ; 



CHOLERA ASIATICA. 181 

( h) caries of neighboring bones (2) ; (i) strangulated hernia (2) ; 
cause unknown in 45 cases. 

Tuberculosis of the appendix, it should be remembered, is 
more common than is generally believed. 

Inflammation of the rectum. Proctitis. The exciting cause of 
this is irritants or the introduction of instruments ; the tendency 
to congestion that exists is a predisposing factor. The inflammation 
is usually chronic and tends to penetrate through the wall, giving 
rise to periproctitis, with abscess formation or even gangrene. 
Abscesses, opening into the bowel or externally, lead to fistulas — 
these are often tuberculous in origin. 

Chronic Inflammation of the Intestines presents two 
stages — the hypertrophic and the atrophic. 

(a) In the hypertrophic stage there is a hyperplasia of the mu- 
cous membrane ; the crypts become tortuous, lengthened, at times 
branching, and in some cases cystic. About the crypts we find a 
round cell infiltration, which in places has been converted into 
fibrous tissue, and by pressure on the glands has caused the cystic 
change. The pressure of the connective tissue also leads to 
atrophy. 

(b) The atropine stage. In this we find the epithelium re- 
moved from extensive areas ; the crypts become small depressions 
only, or are completely destroyed. The portions denuded of their 
epithelium have a map-like appearance. Pigmentation is common, 
sometimes in the hyperplastic and sometimes in the atrophic por- 
tions. Chronic inflammation is frequent in the large intestine, par- 
ticularly in the cecum and ascending colon. Very often the 
hypertrophic and atrophic changes are combined, the former giving 
rise to polypoid projections, especially in the large intestine and 
rectum. 

Infectious Diseases, (a) Cholera Asiatica — This is 

due to the comma bacillus, or spirillum of cholera. 

The lesions of cholera are principally located in the intestinal 
tract ; parenchymatous changes may occur in the other organs, but 
are most marked in the kidney. 

The Intestine. Macroscopy. The peritoneum in death from 
cholera is dry and sticky. The mucous membrane of the bowel is 
diffusely injected and swollen, and presents here and there, particu- 
larly on the projecting portions, minute hemorrhages. In the early 



182 NOTES ON PATHOLOGY. 

stage the intestinal contents consist of a flocculent serous fluid— 
the " rice-water " discharges ; in later stages they are more opaque 
and are described as " meal-soup " discharges. 

In some cases the solitary follicles are especially involved, and 
appear, first as prominent red points, later, in the stage of reaction, 
as whitish projections on the red mucous membrane. The stage 
of reaction in cholera is characterized by a marked cellular pro- 
liferation in the mucous membrane, with a tendency to necrosis. 
The last may be circumscribed to the follicles ; we then have 
minute ulcers, or it may be diffuse, affecting the valvular con- 
niventes. The ulceration may be simple and superficial, or become 
diphtheritic — i. e. } be characterized by a false membrane, the result 
of coagulation necrosis. 

Peyer's patches may be especially involved and may be the 
seat of simple or diphtheroid ulceration. 

Microscopy. In the early stages we have as a characteristic 
feature, a marked proliferation of the epithelial cells of the mucous 
membrane and in the crypts of Lieberkuhn, with a desquamation 
of the cells, and a tendency to hyaline degeneration of the cells 
and the basement membrane. In the bottom of the crypts, among 
the cells, we find the cholera bacilli. These penetrate to a slight 
depth into the basement membrane. They may be present in pure 
culture, both in the mucous membrane and in the intestinal contents. 
The Kidney. The kidney in the early stages of cholera 
presents the characters of acute parenchymatous nephritis; it is 
enlarged, of a violet color, and soft; the cortex is swollen, and the 
entire surface of section looks opaque — as if the organ had been 
" boiled." The same appearance is met with in yellow fever; also 
at times in diphtheria, scarlet fever, and other infectious diseases. 

Microscopy. The epithelial cells are swollen and almost fill 
the tubules ; they are granular in appearance and some show an 
absence of the nucleus. Later the cells may break down into a 
granular mass, which by the aid of a coagulable material is 
converted into tube casts. 

Etiology. The cause of cholera is the comma-shaped micro- 
organism discovered by Koch in 1884. It is introduced with the 
drinking water, although its presence in water has not often been 
demonstrated successfully. Apart from this, the fact that the 
disease spreads down the streams of water is a point in favor of 
the water-borne theory of cholera. 



CHOLERA ASIATICA. 183 

The cholera spirillum, or cholera vibrio , is comma-shaped, shorter 
but thicker than the tubercle bacillus ; its ends are thick, while 
other vibrios have pointed ends ; it is motile, having a single cilium 
at one end ; it is facultatively aerobic, and liquefies gelatin. The 
last two qualities help to distinguish it from other intestinal bacteria 
resembling it, since they are usually anaerobic and non-liquefying. 

Examination of the dejecta or intestinal contents of suspected 
cases. The examination should always be made as soon as 
possible. For this purpose it is best to pour the material into a 
black glass dish. A small flocculus is then picked up and spread 
on a cover-glass, and stained in the usual way, preferably with a 
weak solution of carbol-fuchsin. If nothing is found but a few 
epithelial cells and swarms of vibrios, the diagnosis of cholera can 
be made. But this condition is exceptional, and it is usually neces- 
sary to resort to cultivation, as described below. 

In sending suspected material to a laboratory for examination, 
the use of disinfectants must be avoided. It is best, if the case has 
come to autopsy, to tie a coil oi intestines containing the discharges 
at both ends, and ship it in a perfectly clean bottle, sterilized with 
boiling water. The bottle is then placed in a box of saw-dust im- 
pregnated with mercuric chlorid or carbolic acid. Specimens for 
histologic examination should be placed in alcohol or mercuric 
chlorid solution. 

Cultivation. A flake of material is broken up in a tube of 
liquefied gelatin, and from this tube a second, and from that a third 
is inoculated ; all are then poured into Petri dishes, and the latter 
placed aside at a temperature of from 20 to 24 C. The colonies 
will become apparent in 16 or 18 hours, and when examined 
with a low power lens present a characteristic appearance. They 
form a slight concavity on the surface of the gelatin, this being due 
to the fact that liquefaction occurs so slowly that evaporation can 
keep pace with it. The depression acts as a concave lens ; when the 
lens of the microscope is depressed below the focus, the concavity 
becomes luminous; when it is raised, the image becomes dark. 
Other micro-organisms that might be present, either do not liquefy 
the gelatin at all, or liquefy so rapidly that the concavity is filled 
with fluid. 

The concavity is quite characteristic, but not absolutely so, and 
the positive diagnosis cannot be made as a rule before the end of 24 
hours, at which time the colonies become visible to the naked eye. 



1 84 NOTES ON PATHOLOGY. 

The surface of the gelatin, especially when the plate is held ob- 
liquely to the light, appears as if covered with a large number ot 
vesicles that had been pricked with a needle. Between the 24th 
and 36th hour another characteristic feature appears — the concavity 
presents, when viewed with the microscope, a ground-glass appear- 
ance, as if it were covered with fine, shining granules. The colo- 
nies are not perfectly round. 

In stab cultures in gelatin the cholera vibrio produces in 5 or 
6 days the appearance of a small bubble at the upper part of the 
tube. This is also characteristic, and is due to slow liquefaction 
with evaporation. Hanging-drop and impression preparations 
should also be made. 

The diagnosis of cholera can also be made by a chemical test. 
If ten drops of strong sulphuric acid are added to 8 or 10 c.c. of a 
culture of the cholera vibrio in bouillon or other liquid medium, a 
rose color, gradually deepening into purple, is developed. This is 
the indol-re 'action, and depends upon the fact that the comma bacil- 
lus produces indol and also nitrites which are essential for the devel- 
opment of the reaction when sulphuric acid is added. Several 
other bacteria elaborate indol, but do not produce nitrites, and 
hence do not give the reaction unless nitrites be also added. The test 
should be performed as soon as a pellicle has formed on the surface 
of the culture fluid. 

The growth of the cholera vibrio is associated with the pro- 
duction of two poisons — a nuclein, which is part of the protoplasm 
of the organism, and a toxalbumin, which is elaborated by it. One 
of the poisons produces a septic condition with fever — the symp- 
toms of the later stages of cholera ; the other gives rise to the great 
depression and fall of temperature peculiar to the early stage. 

That the cholera vibrio is the cause of cholera has been proved 
by experiment. Ordinarily, when animals are fed with material 
containing the organisms, they do not take the disease. But if 
prior to the administration the gastric juice is neutralized with an 
alkali, and peristalsis is checked with opium, the animals develop 
cholera. The period of incubation is 48 hours or less. 

Animals can be rendered immune to cholera ; in man experi- 
ments have not been positive. Vaccination of animals is carried out 
as follows : A highly virulent culture is obtained by successive in- 
oculations of the vibrio into guinea-pigs (peritoneal cavity), with 
occasional exposure of the bacterium in culture to the air. Finally, 



TYPHOID FEVER. 



1S5 



the bouillon culture, previously heated to yo° C. to kill the bacilli, 
is inoculated into the peritoneal cavity of a guinea pig — the animal 
will become immune. Haffkin and Klemperer have performed ex- 
periments upon man. Klemperer found that after inoculating him- 
self with the dead virus, his blood was able to render guinea-pigs 
immune ; but he had not determined whether the blood did not 
possess the same property before the inoculation. 

Typhoid Fever. — The disease is due to the bacillus of 
typhoid fever (bacillus of Eberth), infection taking place through 
the food or drink. The period of incubation is not definitely 
established. 

The lesions of typhoid fever are most marked in the intestines. 
On the third or fourth day of the disease we find a general catar- 
rhal inflammation, most pronounced in the region of the ileo-cecal 
valve. At the end of the first week the specific lesions appear ; 
they consist in a special hyperplasia and a peculiar necrosis of the 
lymphoid elements. Peyer's patches and the solitary follicles become 
swollen and red ; soon, however, in the beginning of the second 
week, the cell proliferation becomes so great as to compress the 
vessels and to cause an anemia. The swelling is due to an accumu- 
lation of round cells, and as this in the commencement only affects 
the lymphoid tissue, the latter projects above the connective tissue 
trabecular of Peyer's patches and gives to them a convoluted appear- 
ance. Later the trabecular as well as the surrounding tissues be- 
come infiltrated with round cells, hence the necrotic changes which 
take place at the end of the second and the beginning of the third 
week, extend beyond the confines of the plaques. Toward the end 
of the third week the necrotic tissue is thrown off; during the pro- 
cess perforation of the bowel or of a blood-vessel may occur. The 
typhoid ulcer has the shape of a Peyer's patch — its axis is usually 
longitudinal, sometimes 
transverse ; or it may be 
round from the running 
together of several follicu- 
lar ulcers. 

The lymphatic glands 
of the mesentery are also 
swollen, but are not as a 
rule the seat of necrosis. Here and 
gland may become necrotic, but the 




Typhoid Ulcer. 

there a small portion 



softened area 



of a 

is usually 



1 86 NOTES ON PATHOLOGY. 

absorbed. At times a gland breaks down completely, and by per- 
forating into the peritoneal cavity gives rise to peritonitis. 

The spleen is greatly enlarged. 

In some cases the lymphoid tissue all over the body is involved, 
and ulcers form on the various mucous membranes. 

Etiology. The cause of typhoid fever is the bacillus dis- 
covered by Eberth and subsequently studied by Gaffky. It is 
about the length of the tubercle bacillus, but much broader, some- 
what bent, plump, with rounded ends ; it has a large number of 
cilia projecting from the'sides, and possesses a slow, wavy motion. 
It is facultatively aerobic, does not liquefy gelatin, and grows upon 
all media, but characteristically only on the potato. It stains easily, 
but readily yields up the stain ; it is not stainable by Gram's 
method. Inoculations into lower animals have not been satisfac- 
tory. Bacteria are found in drinking water and in the intestines 
closely resembling the bacillus of Eberth ; this is especially true of 
the bacillus coli communis, and it is held by some that the typhoid 
bacillus is only a modification of this organism. An important 
differential point is that the bacillus coli produces gas while the 
typhoid bacillus does not. Another point of distinction between 
the two, but one not always present, is their difference in growth on 
potato. The typhoid bacillus gives rise to an invisible film, while 
the bacillus coli produces a luxuriant visible growth. The main 
differences between the organisms may be tabulated as follows : 

Bacillus of Typhoid Fever. Bacillus Coli Communis. 

Does not produce gas. Produces gas in media containing glucose, 

lactose, or saccharose. 
Transparent film on potato. Visible growth. 

Does not coagulate milk. Coagulates milk. 

Does not produce lactic acid in media con- Produces lactic acid in such media. 

taining milk-sugar. 
Does not produce indol. Produces indol. 

Motile. Slightly, if at all, motile. 

The typhoid bacillus is readily diagnosed in the tissues, the 
only organisms that might be confounded with it being those of 
putrefaction. When stained with Loffler's alkaline methyl-blue 
solution, the bacilli present themselves as deeply-stained blue masses. 
With an immersion lens it is usually possible to discover individual 
bacilli at the periphery of these masses. 

Distribution in the body. The bacilli are found in the intestinal 
lesions, in the intestinal contents, in the spleen, in the mesenteric 



DYSENTERY. 187 

glands, and in some post-typhoidal cold abscesses. They may also 
occur in the membranes of the brain, and give rise to certain of the 
cerebral symptoms of typhoid fever. 

Sterilized cultures made in thymus gland bouillon have been 
injected for purposes of treatment, but without noteworthy results. 
Sterilized cultures of bacillus pyocyaneus have also been introduced 
into the body of patients, and seemed to lower the temperature and 
cut short the disease. 

Dysentery. — This is a specific inflammation of the lower 
bowel that may be due to a variety of micro-organisms. Three 
forms are described — the catarrhal, the diphtheritic, and the gan- 
grenous. 

(a) Catarrhal dysentery presents no special feature, being the 
same as catarrhal inflammation in the small bowel. The process 
affects particularly the folds of the mucous membrane. 

(b) Diphtheritic dysentery. In this, the most common form, we 
have a marked swelling of the mucous membrane, with coagulation 
necrosis. The casting-off of the necrotic tissue leaves deep, ragged 
ulcers. The process is generally subacute. There is a tendency 
in certain regions to hyperplasia, in others to atrophy, of the mucous 
membrane. This is quite characteristic and is usually associated 
with pigmentation. 

(c) Gangrenous dysentery is rare ; it leads to destruction of one 
or more of the coats of the bowel. 

Etiology. The disease may be produced by irritant ingesta 
(e. g., mercuric chlorid), but is usually due to micro-organisms. 
Many species have been found, but the real cause has not been 
established. With a certain type of dysentery, especially the epi- 
demic form of the tropics, a protozoan, the ameba coli f seems to be 
intimately associated. This resembles the other amebae, being a 
protoplasmic mass, 15 to 30 e> in diameter, therefore larger than 
a leukocyte. It has a nucleus and a granular protoplasm contain- 
ing vacuoles, these being especially numerous when the ameba is 
resting. The ameba may be mistaken for a wandering connective 
tissue or plasma cell. 

Examination. The stools should be examined while still warm, 
as the ameboid movement of the protozoa is then most active and 
renders their detection easy. If a portion of the blood-stained 
mucus is placed in a warmed slide, the ameba will be readily found, 
often in enormous numbers. The organism has been, it is claimed, 



NOTES ON PATHOLOGY. 



successfully cultivated in hay-infusion ; the cultures when injected 
into the rectum of dogs and cats produced dysentery, as do also 
the stools of dysenteric patients. As amebae are found in the 
normal bowel, they cannot be considered the only cause of 
dysentery. 

The amebic dysentery of our climate is usually severe and apt 
to recur. 

Abscess of the liver is a common complication of dysentery. 
In this abscess the ameba may be found alone, perhaps because the 
other organisms have disappeared ; in other cases the ameba is 
associated with pyogenic bacteria ; in still others, the latter alone 
are present. 

Syphilis. — Acquired syphilis is common in the lower rectum 
and about the anus, but rare, if ever occurring, elsewhere in the 
intestine. Congenital lesions, in the form of extensive gummatous 
deposits, are at times found in the jejunum of the new-born. In 
the rectum, syphilis often leads to cicatricial stricture. The anal 
lesions are most common in women, and are condylomas, the result 
of infection by vaginal discharges. 

Tuberculosis is very common and is probably present in all 
cases of advanced pulmonary tuberculosis. Microscopically, the 
lesions are the same as in other parts of the body ; the naked-eye 
appearances are peculiar, the common lesion being a chronic 
ulcer with thickened edges. Gray tubercles can usually be seen on 
the floor of the ulcer. The outline is as a rule transverse to the 
555^55^=-^^ -«-=_— =^ axis of the gut ; but at times 

WkJmk 



it is irregular and may, espe- 
cially when near the ileo- 
cecal valve, resemble the 
typhoidal ulcer. On the 
serous coat we find as a 
Tuberculous uicer. characteristic feature minute 

miliary tubercles which may extend around the bowel, following 
the line of the lymphatics. Cicatrization is rare, probably because 
the patients die before the process can be completed. The ulcers 
show no tendency to perforate. The most common seats of tuber- 
culous lesions are the ileum, in the region of the valve, and the 
rectum. In the rectum perforation is common, and leads to peri- 
proctitis, to ischio-rectal abscess, or to fistula. 




THE LIVER. 189 

Infection is due to the swallowing of sputum by patients suffer- 
ing from pulmonary tuberculosis. 

Tumors Of the Intestines. — These occur chiefly on the 
prominent portions of the bowel, the ileo-cecal valve, the rectum ; 
also at the flexures. 

(a) Adenoma presents itself as a polypoid growth, usually due 
to hyperplasia, or as a flat swelling, the latter being most frequent 
in the rectum, just above the area of squamous epithelium. 

(b) Carcinoma is generally cylindrical, and adenomatous in 
character. It is most frequent in the rectum, the cecum, and the 
flexures of the colon. Although rare in the small intestines, it 
occasionally occurs in the duodenum, at the entrance of the biliary- 
pancreatic duct. The cylindrical cancer appears either in the form 
of fungoid masses or as polypoid projections, and has a strong 
tendency to ulcerate. The epithelium is columnar and nicely 
arranged in a manner strongly suggestive of adenoma. Squamous 
cancer is found at the lower portion of the rectum and about the 
anus. It is apt to give metastasis to the inguinal glands. 

(b) Sarcoma is rare as a primary, but more common as a sec- 
ondary growth. 

(c) Lipoma, and (d) myxoma grow from the submucous or sub- 
serous areolar tissue. 

THE LIVER. 

Anatomy. The liver is the largest glandular organ of the body, 
weighing about 1500 grams. It is made up of lobules or acini, in 
the center of which is the opening of the central vein, a branch ol 
the hepatic vein. Radiating from this we have the liver cells — 
large epithelial cells containing a large vesicular nucleus and 
granular protoplasm. At the periphery of the acini we find the 
branches of the portal vein, the hepatic artery, the bile duct, and 
the lymphatics, all held together by delicate connective tissue, the 
capsule of Glisson. There are two currents of fluid in the liver — 
the one, in the portal vein and hepatic artery, from the periphery 
of the lobule to the center to empty into the central vein, the other, 
that of the lymph and bile, from the lobule outward to empty into 
the perilobular vessels. 

Functions, (a) The liver elaborates bile which aids in digestion, 
as it contains a fat-emulsifying substance and a diastatic ferment ; it 
promotes the absorption of the products of digestion through the 



190 NOTES ON PATHOLOGY. 

intestinal walls, stimulates peristalsis, and acts as the natural anti- 
septic of the bowel, {b) The liver has important nutritive or 
metabolic functions, which are not yet thoroughly understood. It 
manufactures glycogen, a starch-like body, which is converted into 
glucose by a ferment present in the blood. The sugar thus pro- 
duced is under normal conditions rapidly oxidized, and no excess 
occurs in the blood. In certain pathologic states, as in diabetes, 
the blood becomes surcharged with sugar, which in part passes off 
with the urine. This accumulation of sugar may be due to an 
increased formation, probably brought about by the blood remain- 
ing longer in the liver than normally, or to an imperfect action of 
the oxidative processes by which sugar is normally destroyed, (c) 
The liver also possesses certain eliminative functions, and (d) is 
concerned in the neutralization of many poisons absorbed from 
the digestive tract. 

Disturbances Of Circulation.— (a) Active congestion oc- 
curs physiologically as the result of over-feeding ; it is also seen in 
diabetes, and it is probable that the form of diabetes brought about 
by injury or disease of the floor of the fourth ventricle, is due to 
congestion of the liver. A similar congestion results from section 
of the sympathetic fibers going to the organ. 

(b) Passive congestion is the result of heart and lung disease, 
and usually appears very early since the hepatic vein empties almost 
directly into the right auricle. The first effect is the overfilling of the 
central vein ; the surrounding lobule subsequently undergoing vari- 
ous changes. If it becomes fatty, we get the condition of " nutmeg 
liver," or " fatty nutmeg liver," so-called on account of the contrast 
presented by the dark central vein and the light periphery. In 
other cases, the hepatic cells atrophy, either as a primary change 
or secondarily to the fatty degeneration. We have then a dark 
center surrounded by a grayish lobule consisting chiefly of connec- 
tive tissue, the increase of which is partly relative, from atrophy of 
the parenchyma, partly due to active hyperplasia. Such a liver is 
known as " atrophic nutmeg liver." Finally, there may be cases in 
which the peripheral parts of the lobules are also congested and 
are the seat of the deposit of blood pigment. 

Infiltrations and Degenerations.— (a) Pigmentary infil- 
tration is very common, particularly in the periportal connective 
tissue; in advanced cases the liver cells are also affected. The 
pigment consists of reddish-brown or orange-colored granules of 



ACUTE YELLOW ATROPHY. 191 

hemosiderin. The causes of pigmentation are (a) malaria and (j3) 
pernicious anemia, both bringing about a destruction of the red 
corpuscles ; also (y) passive congestion. In pernicious anemia the 
pigment may be colorless ; it contains iron, and therefore turns 
black when the section is treated with (NH 4 ) 2 S. 

(b) Fatty infiltration is normal in the liver, but is also very 
frequent as a pathologic change. In mild cases the fat is deposited 
at the periphery of the acini in the form of large, shining droplets, 
in severe cases all the cells may be filled with drops of fat. The 
liver is enlarged, anemic, and either uniformly yellow or streaked 
with pale lines. The causes of fatty infiltration are general obesity, 
pulmonary tuberculosis, and the abuse of alcohol. 

(c) Fatty degeiieratio?i is produced by infectious fevers, poisons, 
and grave anemias, and also accompanies advanced cases of fatty 
infiltration. In the infectious fevers it is generally preceded by 
cloudy swelling. 

(d) Amyloid degeneration is common in the liver and is gen- 
erally associated with amyloid disease in other organs, being due to 
chronic suppuration, as in tuberculous and syphilitic bone disease. 

Acute Yellow Atrophy is an acute disease characterized by 
a rapid degeneration of the liver cells, beginning as cloudy swelling 
and quickly passing on to fatty degeneration, breaking-down and 
removal of the cells. The liver is greatly reduced in size, soft, 
almost fluctuating, and variegated in color, presenting areas that 
are yellowish from fatty change and others red from congestion 
and hemorrhage. Microscopically, we find the evidences of an in- 
tense fatty degeneration, the outline of the cells is lost, the nuclei 
have disappeared, and the protoplasm is converted into fat granules, 
which may coalesce to form droplets. In places there is marked 
congestion, with hemorrhage from the capillaries and the deposition 
of blood pigment. The presence of an excess of blood is quite 
characteristic of acute yellow atrophy. Crystals of leucin and 
tyrosin are present. 

Etiology. The cause is not definitely known, but it is probable 
that it is an acute infection. In phosphorus and arsenic poisoning 
the liver may present a condition resembling that of acute yellow 
atrophy. The process is, however, less acute. 

Inflammations, i Acute Interstitial Hepatitis, 
Acute Suppurative Hepatitis. Abscess. — Abscess is 

always micro-organismal and may be due (a) to infection along 



192 NOTES ON PATHOLOGY. 

the bile ducts, after obstruction of the latter by gall-stones, or by 
extension of infection from the duodenum ; (b) to pyemia ; (c) to 
extension of a suppurative process from neighboring organs, as the 
peritoneum, pleura, stomach, or intestines ; (d) to wounds ; (e) to 
dysentery. 

The abscess of the liver due to dysentery is usually a single, 
large, deep-seated abscess, rarely consisting of two or three com- 
municating cavities. As already stated, it may be associated with 
the presence of the ameba coli or of the pyogenic organisms, or of 
both simultaneously. The pyemic abscesses are multiple, small, 
and situated near the periphery of the organ. 

Histologically, we find, as in all other organs, that the archi- 
blastic tissues break down rapidly, undergoing first cloudy swelling, 
later coagulation necrosis and fatty degeneration. 

2. Chronic Interstitial Hepatitis, or Cirrhosis, is 
characterized by a hyperplasia of the connective tissue, involving 
especially the connective tissue between the acini. If the acini 
become involved, the change affects as a rule only their peripheral 
portions, the center remaining healthy. Histologically, we find the 
following : (a) round cell infiltration, (b) formation of new connective 
tissue, (c) multiplication of the biliary passages, (d) atrophy of the 
liver cells, chiefly at the periphery of the acini. 

Two forms of cirrhosis are described, the atrophic and the 
hypertrophic. 

(a) Atrophic Cirrhosis. — In this we have an overgrowth 
of the connective tissue with a tendency to contraction. The hyper- 
plasia is chiefly perilobular, or "periportal," and does not as a rule 
penetrate into the acini. 

The process is very slow, and although there is a marked round 
cell infiltration in the early stages, the liver is not made larger, as 
contraction in one part goes hand in hand with proliferation in 
another. At an early period, before the cirrhosis has actually 
begun, the liver may be enlarged somewhat from congestion and 
fatty infiltration. In the later stages the organ is always reduced 
in size. 

Macroscopy. The surface of the liver is finely granular or 
marked by coarse projections (" hob-nail liver "), depending upon 
whether the connective tissue surrounds a single or several lobules. 
On section we see the acini sharply outlined by grayish bands of 
fibrous tissue ; in the center of the acini the liver cells still preserve 



ATROPHIC CIRRHOSIS. 



193 




Atrophic Cirrhosis of Liver. 



their normal yellowish color. The organ is firm, small, and cuts 

with considerable difficulty. Microscopically, the connective tissue 

fs seen to be rich in blood-vessels, and 

shows even in the later stages a round cell 

infiltration. There is also a hyperplasia of 

the bile- ducts, new tubules being scattered 

through the connective tissue. This is a 

strange phenomenon not easily explained. 

The liver cells at the periphery of the acini 

are atrophic and may be fatty. 

Results. The hyperplasia and con- 
traction affect chiefly the branches of the 
portal vein running in the perilobular tissue, and necessarily inter- 
fere with the circulation through these vessels. Passive congestion 
in the area drained by the portal vein results and causes the major- 
ity of all the symptoms of cirrhosis. There is congestion of the 
gastro-intestinal tract (hemorrhoids, hemorrhages from stomach or 
intestines), ascites, and collateral dilatation of small veins in the 
abdominal wall which attempt to carry the blood from the intestines 
to the vena cava. The spleen is also enlarged from passive con- 
gestion. 

The hepatic artery and its branches are not involved ; as the 
biliary passages also escape, jaundice is but rarely present. 

Etiology. In regard to the causes of cirrhosis of the liver 
(as well as of other organs) we meet with the same difference of 
opinion as that to which allusion was made in the chapter on 
primary degenerations of the nervous system. According to one 
theory, the primary change is a degeneration of the liver cells, the 
connective tissue remaining relatively in excess or undergoing a 
secondary hyperplasia. According to another theory the connec- 
tive tissue hyperplasia is primary and the archiblastic changes sec- 
ondary. Both theories are probably correct, some cases being 
explicable by the first, others by the second. 

Thus in the cirrhosis following phosphorus poisoning there is 
no doubt a primary degeneration of the cells, the excess of con- 
nective tissue being in part relative, in part an actual overgrowth. 
Again, in the cirrhosis accompanying chronic obstruction of the 
bile-ducts, there is a primary atrophy of the liver cells from pressure 
by the distended biliary passages, the connective tissue becoming 
secondarily hyperplastic. The same thing is true of cirrhotic 

13 



194 NOTES ON PATHOLOGY. 

conditions following other forms of pressure (tight lacing, pressure 
of tumors, etc.). 

In the ordinary form of cirrhosis, however, there is unquestion- 
ably a primary hyperplasia of the connective tissue, the atrophy and 
degeneration of the parenchyma being a secondary occurrence. 

The cause of the connective tissue hyperplasia is usually the 
presence of irritant substances in the portal blood, the most com- 
mon being alcohol. In other cases the irritant is not known, 
the cirrhosis in these instances being a part of a general sclerotic 
process, affecting the arteries, the liver, kidney, and heart. The 
irritant is probably of metabolic origin, its elaboration being favored 
by old age. 

Hypertrophic Cirrhosis is an entirely different disease and 
is characterized by hyperplasia of the connective tissue throughout 
the organ, without a tendency on the part of the new tissue to con- 
tract. The hyperplasia occurs in successive attacks, each attack 
being accompanied by fever, pain, increase in the size of the organ, 
and jaundice. 

Macroscopy. The organ is enlarged, smooth, firm, olive-green 
in color, or light-green when fatty degeneration is also present. 

Microscopy. There is a prominent round cell infiltration, both 
periportal and between the liver cells of the acini ; the tendency to 
the formation of connective tissue is slight. There is also a marked 
hyperplasia of the bile-ducts, greater, indeed, than in the atrophic 
cirrhosis. 

Results. There is no interference with the portal circulation, 
hence dropsy is absent. The biliary capillaries, on the other hand, 
are greatly compressed by the presence of the round cell infiltra- 
tion between the liver cells ; jaundice is, therefore, common. 

Etiology. The causation of hypertrophic cirrhosis is obscure ; 
the disease is more common in the Southern States, and may be 
infectious. 

Tuberculosis of the liver is not common ; when it occurs, 
it is usually miliary, the tubercles being as a rule so small that they 
are only demonstrable with the microscope. Cheesy nodes are 
very rare. 

Syphilis is rare in all viscera, but is perhaps relatively more 
common in the liver than in any other viscus, the usual lesion being 
the gumma. 



TUMORS. 19$ 

Tumors. — Primary tumors are less common than secon- 
dary. 

(a) Adenoma is quite a frequent primary growth. It is gen- 
erally multiple, small in size, rarely larger than a cherry, and as a 
rule is situated near the periphery of the organ. It is grayish in 
color or if very vascular, reddish. Microscopically, the adenoma is 
of the tubular variety, which is not strange when we remember that 
the liver is primarily a tubular gland, as may be seen in the human 
embryo, in some of the lower animals, and even on careful study in 
the adult human liver. 

(6) Cystic adenoma springs from the small mucous glands of 
the bile ducts, is multiple, and as a rule larger than the simple 
adenoma. 

(c) Cancer is rare as a primary, but very frequent as a sec- 
ondary growth. Primary cancer appears in three forms : 

1. Massive cancer — single, large, circumscribed masses, resem- 
bling secondary growths. When metastasis takes place, the 
secondary nodes are found also in the liver, in close proximity to 
the primary tumor. 

2. Diffuse cancer with cirrhosis, or cirrhotic cancer. The liver 
presents a marked overgrowth of connective tissue, through the 
meshes of which the cancer nests are scattered. The disease 
is distributed uniformly throughout the organ. 

3. Periportal ca?icer. This is characterized by the development 
of cancer about the branches of the portal vein, beginning at the 
entrance of the vein and presenting the largest mass at the trans- 
verse fissure, and thence accompanying the vessel to its finest 
branches. It is distinguished from cirrhotic cancer by the fact that 
it begins at the entrance of the large vessels and extends to the 
smallest, while the latter is first found as a rule in the connective 
tissue between the acini, in the region of the small portal veins. 

The cells of cancer of the liver are generally polymorphous ; 
occasionally cancers containing only cylindrical cells are found. 

Secondary cancer appears in the form of multiple, circum- 
scribed, whitish nodes, contrasting markedly with the dark liver 
substance. The larger nodes possess a capsule. Softening is quite 
common in the interior of the growths, and leads to a depression of 
the surface — a condition known as " umbilication " — which is also 
observed, though more rarely, in the primary cancer of the first 
variety. 



196 NOTES ON PATHOLOGY. 

Metastatic cancer is generally secondary to carcinoma of the 
stomach, in which case the nodes possess the characteristics just 
given. If the metastasis is from a cancer of the esophagus or the 
breast, the secondary growths are generally infiltrating and not 
encapsulated. 

Sarcoma is rarely primary ; as a secondary growth, the melan- 
otic sarcoma is the most frequent, being generally secondary to a 
similar tumor in the eye. The metastatic growths are as a rule 
pigmented like the primary, but, rarely, there may be a kind of 
double metastasis, some of the secondary nodes being pigmented, 
others not. In most instances the other abdominal viscera are also 
involved in the metastasis. 

Angioma is the most frequent simple tumor of the liver, and is 
of the cavernous type. It occurs especially in the old, and does not 
impair the function of the liver ; therefore, it is rarely diagnosed 
during life. It is small, circumscribed, dark in color, and is gen- 
erally situated on the surface of the organ. There may be two or 
three tumors, rarely more. 

Fibroma is quite rare. A few cases of ?teuro-Jibroma t i. e., a 
fibroma extending along the nerves of the liver, have been 
described. 

THE BILIARY PASSAGES. 

Biliary Calculi. — This is the most important morbid condi- 
tion affecting the biliary passages. Calculi are most frequently 
found in the gall-bladder, but are met with elsewhere in the pas- 
sages, either in the common duct or in the branches higher up. In 
size they vary from minute granules to large masses. They may 
be single, when they are round and smooth ; or multiple, when they 
are faceted from mutual pressure. Their color varies from light- 
yellow to a deep greenish-black. The center is usually dark, even 
in the light-colored stones, and is surrounded by a paler area having 
a crystalline or radiating arrangement. The center or nucleus is 
composed of inspissated bile, which may form the whole of the 
stone, but as a rule the outer layers consist of cholesterin. 

Causes. Two factors appear to be necessary — a central nucleus 
and an altered composition of the bile. The nucleus is usually a 
foreign body, either something from the intestines or a mass ot 
loosened epithelial cells. The change in composition, the more 
important factor, results from stagnation of the bile in its passage to 



THE BILIARY PASSAGES. 197 

the intestines. The bile becomes inspissated, and the cholesterin, 
which normally is held in solution by the salts of the biliary acids, 
is precipitated on account of a deficiency of these salts. Perhaps 
bacteria are concerned in the production of these chemical changes. 

Effects of gallstones. Pain is the most prominent symptom 
attending their passage. When they obstruct the duct, jaundice 
results from absorption of the bile. The irritation of a calculus 
may lead to inflammation or ulceration of the duct, or even to per- 
foration. Perforation may take place into the bowel, and this is the 
only way in which the escape of very large stones can be explained. 
It may also occur into the peritoneal cavity or externally. 

The passages above an impacted stone become dilated, and this 
dilatation is apt to lead to connective tissue hyperplasia, or cirrhosis, 
around the ducts. 

Inflammation of the Bile Passages.— (a) Mild or 
catarrhal forms are very common, being usually due to extension 
of inflammation from the duodenum. The mucosa may be so 
swollen, or mucus may accumulate to such an extent, that obstruc- 
tion and jaundice result. Recovery, without permanent lesion, is 
the rule. 

(d) There may be severe inflammation, with tendency to sup- 
puration and ulceration. This is apt to occur in cases of gallstone. 
Bacteria no doubt play an important part in those inflammations. 
Under normal conditions the bile destroys the bacteria which have 
ready access to the bile passages from the intestines. In cases of 
disease, however, many organisms are found in the bile. They may 
be the starting point of the chemical changes through which gall 
stones are formed. 

These severe inflammations may lead to septicemia or pyemia ; 
or obstruction may result from cicatricial contraction and give rise 
to cystic changes of the gall bladder or ducts, or to a cirrhotic con- 
dition of the liver. 

Tumors. — Cancer of the liver may spring from the bile 
passages. 



I9« NOTES ON PATHOLOGY. 



CHAPTER XII. 



THE RESPIRATORY ORGANS. 

THE NASAL CAVITIES. 

The nasal cavities are lined by columnar ciliated epithelium ; 
the upper part of the mucous membrane is olfactory, the lower 
respiratory. Mucous glands are present in great abundance. The 
submucosa is erectile, particularly in the region of the lower turbi- 
nated bones. 

Circulatory Disturbances. — (a) Congestion of the erectile 
tissue precedes inflammation, but also occurs periodically from 
obscure causes, and gives rise to curious reflex symptoms, as 
asthma, cough, epilepsy, ocular and uterine disturbances. 

(b) Hemorrhage. Epistaxis. This may be due to the periodic 
congestion just described, to passive congestion from heart disease, 
to liver disease, to the hemorrhagic diseases, like hemophilia and 
scurvy, to infectious diseases, or it may be vicarious. 

inflammation. Acute Rhinitis or Coryza. — All acute 
inflammations of the nose are of bacterial origin, the bacteria being 
those that are normally present in the nasal mucus. Even the 
tubercle bacillus has been found in healthy nasal mucous mem- 
branes. 

Coryza is characterized by a marked proliferation and desqua- 
mation of cells, which undergo a rapid mucoid degeneration. The 
exudation is at first thin — sero-mucous — containing ciliated epi- 
thelium and a few leukocytes. Later it becomes more purulent. 
The process may extend to the sinuses communicating with the 
nose or to the larynx and trachea. 

Etiology. As already stated, the true cause is bacteria ; cold, 
however, plays an important part, but just how it acts, is not defi- 
nitely known — perhaps by altering the character of the secretion it 
prepares the mucous membrane for the infection. The disease is 
communicable from one individual to another. 

Suppurative rhinitis is due to infection with the glanders 
bacillus or the gonococcus, or to extension of suppuration from the 
neighboring tissues, as the bones. 



THE NASAL CAVITIES. 199 

Chronic Rhinitis is the result of frequent attacks of acute 
rhinitis, or of certain infections, as tuberculosis, syphilis, and chronic 
glanders. Two varieties are recognizable : the hypertrophic and 
the atrophic. In the hypertrophic the mucous membrane is thick- 
ened from a hyperplasia of the connective tissue, the epithelium, 
and the mucous glands. The hyperplasia may be circumscribed 
and give rise to tumor-like masses termed polyps. The atrophic 
form is a secondary process, being the result of the contraction of 
the hyperplastic connective tissue or of the healing of ulcers. 

Ozena is a form of chronic rhinitis accompanied by fetid dis- 
charges. It is generally due to syphilis or tuberculosis involving 
the bones, but may be the result of an atrophic rhinitis with ulcer- 
ation. 

Syphilis may give rise to condylomata, or to gummata affecting 
the cartilages, bones, periosteum, or perichondrium, the breaking- 
down of which produces extensive destruction; it may also lead to 
a hyperplastic form of rhinitis, which terminates, like the simple 
hypertrophic, in atrophy and ozena. 

Tuberculosis occurs in the form of miliary tubercles or tuber- 
culous ulcers, the latter being more common than is generally 
assumed. It is possible that these nasal lesions may be the source 
of meningeal tuberculosis in children. 

Occasionally, lupus of the face extends inward to the nasal 
mucous membrane. 

Glanders is common in the nasal mucous membrane of the 
horse ; it has a marked tendency to cause suppuration, and runs 
an acute course, ending in death. In man the disease affects the 
nose less frequently, and is more chronic. 

Tumors. — (a) Mucous polyps are the most frequent tumors in 
the clinical sense, but, pathologically, the majority must be con- 
sidered inflammatory hyperplasias of all the structures of the mucous 
membrane, with myxomatous degeneration in the epithelium. Very 
often they are cystic from occlusion of the glands and distention of 
these by mucoid secretion. In rare cases the polyp is a true tumor, 
a myxoma. The most frequent seat of polyps is about the middle 
turbinated bone. They tend to recur after removal. 

(b) Fibroma, hard and soft, spring from the basilar process of 
the occipital and sphenoid bones. 

(c) Chondroma, osteo-chondroma, and osteoma, are rare; they 
occur most frequently in the sinuses. 



zoo NOTES ON PATHOLOGY. 

(d) Sarcoma may develop on the septum or the posterior parts 
of the nasal cavity. 

(e) Cancer is rare, and is usually a squamous epithelioma 
extending inward from the face. 

THE LARYNX. 

Anatomy. The mucous membrane of the larynx is covered in 
greater part by columnar ciliated cells, but on the epiglottis there 
are patches of squamous epithelium, from which, as a center, pro- 
cesses of squamous epithelium radiate downward toward the true 
vocal cords ; the latter are covered entirely by squamous cells. 

Malformations of the larynx are not common. As the result 
of imperfect union of the branchial clefts, fistulas may arise, al- 
though these are more frequent in the pharynx. 

Hypoplasia of the larynx may occur. A condition termed 
" emphysema of the neck " is due to dilatation of the ventricles 
of the larynx. 

Circulatory Disturbances.— (a) Active hyperemia is com- 
mon, but rarely shows after death, on account of the squeezing out 
of the blood by the contraction of the elastic tissue, which is very 
abundant in the larynx. 

(J?) Passive hyperemia is due to valvular heart disease. 

(c) Hemorrhage ', in the form of minute, pin-point size extra- 
vasations, occurs in acute inflammations, in death from suffocation, 
and in the purpuric diseases. 

(d) Edema of the glottis may be due to Bright's disease or heart 
disease, but most commonly is caused by inflammatory processes, 
especially when these are deep-seated and accompanied by ulcera- 
tion. It affects the loose cellular tissue at the base of the epiglottis ; 
also the false vocal cords and the ventricles. This form of edema 
is not a passive transudate, but is inflammatory and is accompanied 
by an extensive leukocytic infiltration ; in some cases it is purulent. 

Inflammation. — (a) Acute catarrhal laryngitis is character- 
ized by congestion and punctiform hemorrhages in the mucous 
membrane, by an increased secretion of mucus, and by desquamation 
and mucoid degeneration of the epithelial cells. Superficial ulcers 
may form. In some cases the inflammation is chiefly follicular, the 
swollen follicles standing out first as reddish, later as whitish points. 
They may break down and form deep ulcers. The follicular form 
affects particularly the epiglottis, the aryepiglottic folds, the false 



THE LARYNX. aoi 

vocal cords, and the ventricles. The causes of acute laryngitis are 
infectious diseases, such as measles, small-pox, influenza, typhoid 
fever, and irritating vapors ; it may also occur in association with 
chronic ulcerative processes. 

(b) Chronic laryngitis presents itself in two forms : (i) the hyper- 
trophic and (2) the atrophic. In the first the mucous membrane 
and submucous tissue are greatly thickened, forming in places 
warty projections, " pachyderma laryngis." The atrophic form is due 
to the contraction of the new tissue with the formation of cicatricial 
bands, and is usually secondary to ulceration. Deformity of the 
larynx may be produced and lead to interference with speech. 

(c) Croupous laryngitis. The formation of false membranes in 
the larynx is usually due to the bacillus of diphtheria, but may be 
brought about by irritants, as steam, and by other micro-organisms, 
as that of typhoid fever. Typhoid fever may also cause a simple 
catarrhal inflammation. 

-Diphtheria of the larynx is usually secondary to pharyngeal 
diphtheria, and is a more superficial process. The larynx does not 
possess a very loose submucous connective tissue nor an abundant 
lymphatic supply, hence absorption is not active, and constitutional 
symptoms not marked. The local symptoms are, on the other hand, 
very severe, and death often results from suffocation. The disease 
may extend down the bronchial tubes ; by the inhalation of infected 
particles, broncho-pneumonia may be set up. 1 

(d) Suppurative lary?igitis. This may be (1) a purulent infil- 
tration analogous to edema, or (2) it maybe in the form of localized 
abscesses. The process at times extends to the perichondrium, 
inducing a suppurative perichondritis which in turn leads to destruc- 
tion of the cartilages. Portions of these may become separated, 
and, falling over the glottis, cause death by suffocation. Perichon- 
dritis is usually connected with chronic ulceration, as from syphilis 
and tuberculosis, but may be due to typhoid fever or diphtheria. 

Tuberculosis is very common. Although it may be primary, it 
is in the vast majority of cases secondary to tuberculosis of the 
lung, infection taking place either through the blood or through 
the sputum. The lesions usually begin in the posterior wall, 
between the arytenoid cartilages and in the aryepiglottic folds, 
although they are not circumscribed to these regions. The tuber- 
cles are primarily submucous, and give rise at first to a simple 

1 For details concerning the bacillus of diphtheria see Pharyngeal Diphtheria., in Chapter XI 



a>« NOTES ON PATHOLOGY. 

swelling ; later, running together, they break down and lead to the 
formation of slowly-healing ulcers. Eventually the ulceration may 
extend to the perichondrium and cartilages. That healing of such 
ulcers is possible, has been proved ; but while cicatrization proceeds 
in one region, the disease spreads in another, consequently com- 
plete cure is very rare. This was demonstrated during the tuber- 
culin treatment. 

Lupus is a rare form of tuberculosis of the larynx, and is 
generally an extension of lupus of the pharynx, where it may be 
primary. 

Syphilis is less common than tuberculosis, and differs also in 
the fact that it is usually a downward extension from the pharynx 
(like lupus), while tuberculosis begins below and travels upward. 
The extension is along the anterior wall ; this, together with the de- 
cided tendency to cicatricial contraction, is quite diagnostic of syphilis. 

The disease presents itself in the form of mucous patches, 
gummy tumors, and simple catarrhal inflammations. The last are 
not characteristic, but are ordinary catarrhal inflammations, seem- 
ingly kept up by the syphilitic poison. 

Tumors, (a) Papilloma. There is in the larynx, as in the nose, 
a marked tendency to hypertrophy of the mucous membrane ; the 
tumors, however, are not as a rule polypoid, i. e. f myxomatous, but 
are papillomatous. Two varieties of papilloma are described, the 
hard and the soft. In the former we have a tendency to the 
formation of hard, horny excrescences, consisting of the hyper- 
trophy of the papillae and a thickening of the epithelium, and pro- 
ducing a pachydermatous condition {pachyderma laryngis). In the 
soft the hypertrophy affects mainly the papillae, and gives rise to 
extensive dendritic growths, covered only by a thin layer of epi- 
thelium. These are termed acuminate condylomata, or " warts of 
the larynx." The soft condylomas may at times be true myxomas, 
and grow from the interior of the ventricles. 

Papillomata occur especially about the true vocal cords, but 
may extend upward to the epiglottis, and also downward, having a 
tendency to cause " squamous invasion," that is, to induce a trans- 
formation of the columnar epithelium into the squamous variety. 
Papillomata constitute 67 per cent, of all laryngeal tumors, and 
are usually due to repeated irritation, such as is caused by smoking 
or speaking, or they maybe developed about the borders of chronic 
ulcers. 



THE BRONCHIAL TUBES. 203 

(3) Fibroma may be hard or soft, and grows most frequently 
from the vocal cords, the aryepiglottic folds, the base of the epi- 
glottis, and the ventricles. It is generally single, but may present 
numerous excrescences. 

(c) Myxoma is rare. 

(d) Sarcoma is a rare growth in the larynx, but a primary 
spindle-cell sarcoma sometimes springs from the epiglottis. 

(e) Carcinoma is common, and is either the result of extension 
from the esophagus, the tongue, or other neighboring part, or is 
primary, occurring about the true vocal cords, at the entrance of 
the ventricles. It appears as if the papillomatous tumors at times 
take on an epitheliomatous formation. 

Cancer is usually squamous, but may be cylindrical. The 
papillomatous excrescences surrounding the cancer may give rise to 
errors in diagnosis. 

THE BRONCHIAL TUBES. 

Anatomy, The bronchial tubes are a system of dichotomously 
dividing tubes lined by mucous membrane, on the outside of which 
is connective tissue containing cartilaginous plates, smooth muscle 
tissue, and elastic fibers, the last being especially abundant where 
the cartilaginous rings are incomplete. The bronchi are abundantly 
supplied with racemose mucous glands extending deeply, even into 
the cartilages. The epithelium is columnar and ciliated down until 
tubes of one millimeter caliber are reached, when the epithelium 
loses its cilia and becomes cuboidal, while the tubes themselves are 
deprived of their cartilages and mucous glands. The terminal 
bronchioles open into the air-passages, which in turn open into the 
infundibula. In the walls of the latter we find the air-vesicles, lined 
with a flat epithelium. 

Hyperemia may be active or passive — the former occurring 
in the early stages of inflammation, the latter as a consequence of 
disturbances in the general or the pulmonary circulation, especially 
from valvular heart disease. Active hyperemia is apt to disappear 
after death. 

Inflammation. Acute Bronchitis is due to irritants, 
particularly to exposure to cold. The catarrhal form is character- 
ized by congestion, swelling, and opacity of the mucous membrane, 
an increased secretion of mucus, and punctiform hemorrhages. 
In rare cases the racemose glands, which usually are invisible, 



ao4 NOTES ON PATHOLOGY. 

are especially involved, causing a follicular catarrhal inflammation. 
The exudate is at first thick and tenacious, consisting chiefly of 
mucus ; later it becomes more liquid, and, from an admixture ot 
pus, yellowish in color. In some cases the exudate is liquid and 
very abundant, and gives rise to serous bronchitis or bronchorrhea. 

Microscopically, we find proliferation, desquamation, and de- 
generation of the surface epithelium, together with evidences of 
true inflammation of the submucous connective tissue, namely, a 
round cell infiltration and a dilatation of the blood-vessels. If the 
outwandering of the leukocytes is marked, the exudate becomes 
muco-purulent or purulent. 

Croupous Bronchitis may be the result of the extension 
of a croupous laryngitis, being due to the Klebs-LofBer bacillus, 
but this form rarely becomes a prominent feature. There is another 
variety which comes on periodically in certain individuals who may 
or may not be the subjects of chronic bronchitis. They are sud- 
denly seized with violent cough and dyspnea, which last four or five 
days, and are relieved by the expectoration of fibrinous membranes, 
i. e. casts of the bronchial tubes. In the substance of these casts 
we find Charcot-Leyden crystals and eosinophile cells. 

In many cases of asthma a similar condition exists — a coagu- 
lation necrosis affecting the smaller bronchial tubes, and giving rise 
to the expectoration of spiral fibrinous coagula having the shape ol 
twisted bands, and containing Charcot-Leyden crystals and eosino- 
phile cells. 

Chronic Bronchitis results (a) from frequently repeated 
acute attacks. 

(b) From disturbances in the circulation of the lungs. Under 
this head come (i) the bronchitis occurring in the old. One ot 
the first evidences of advancing age is " loss of wind," associated 
with imperfect circulation in the lungs. (2) The bronchitis depen- 
dent on congestion due to valvular heart disease. (3) The chronic 
bronchitis of childhood, associated with engorgement of the lym- 
phatic glands and lymphatic channels. 

(c) Tuberculosis of the bronchial tubes or of the lungs. 

(d) Peribronchitis. All forms of chronic bronchitis are accom- 
panied by peribronchitis, and even in the acute there is a slight 
degree of peribronchial inflammation. In some cases the peri- 
bronchitis is primary, and forms the starting-point of a chronic 



OBSTRUCTION OF THE BRONCHIAL TUBES. 205 

bronchitis. Two forms of peribronchitis may be described : the 
fibrous and the suppurative. Both extend inward from the pleura, 
either that of the hilum (the bronchial glands) or that in contact with 
the costal pleura. In the fibrous form there is a marked thickening 
outside of the bronchial tubes. The suppurative is the result of 
extension of a suppurative process in the pleura along the lym- 
phatics, the subpleural lymph channels being first involved. A 
similar appearance is produced by engorgement of the subpleural 
and pulmonary network of lymphatics, but the lines of injection 
are somewhat paler, and on section exude clear lymph. The cause 
of this engorgement is pressure, chiefly by an hypertrophied heart, 
on the mediastinal and bronchial lymphatic glands. At times the 
condition resembles miliary tuberculosis in appearance, but is dis- 
tinguished by the presence of fluid on section. 

Chronic bronchitis has two stages : a hypertrophic and an 
atrophic stage. In the former there is swelling of the mucous 
membrane, cellular infiltration of the submucous tissue, hyper- 
plasia of the glands, and a tendency to dendritic formation. The 
atrophic is a terminal stage of the hypertrophic, and may follow 
with or without preceding ulceration. There is either complete 
absence of the epithelial lining or the formation of an irregular 
cuboidal or even squamous epithelium. 

Tuberculous bronchitis affects especially the smaller tubes, and 
gives rise to a desquamative process, resulting in an abundant 
accumulation of cells without the presence of much fluid. The 
cellular masses undergo caseous change, and eventually liquefac- 
tion, and are discharged, leaving tuberculous ulcers. The process 
may then extend to the surrounding tissues and set up a tuberculous 
peribronchitis, or tuberculosis of the lung substance proper. 

The macroscopic appearance of the cases in which the disease 
began in the bronchi is characteristic, and should always be recog- 
nized. On examination the cut surface of the lung presents little 
projecting masses, each with a central opening, which is the 
bronchial tube. The walls of the tube are thickened from bron- 
chitis and also from peribronchitis. As a rule, the peribronchial 
hyperplasia shares in the caseation, but in some cases it goes on to 
the formation of fibrous tissue (fibrous peribronchitis), a process by 
which healing may be brought about. 

Obstruction of the Bronchial Tubes may be acute or 
chronic, (a) Acute obstruction is generally due to an accumulation 



2o6 NOTES ON PATHOLOGY. 

of mucus and to swelling of the mucous membrane in acute bron- 
chitis. It may lead to atelectasis, to catarrhal pneumonia, or to 
acute emphysema. 

Acute emphysema is brought about in the following way : The 
obstruction acts as a valve permitting the entrance but not the exit 
of air. Efforts of coughing, not being able to expel the confined 
air, will induce a dilatation of the air-vesicles, and at times minute 
ruptures in their walls, with the production of interstitial emphy- 
sema. Atelectasis, following obstruction of a bronchus, may be the 
result of a valve-like action on the part of the obstructing body, 
which permits the exit but not the entrance of air. This is excep- 
tional ; the more frequent cause of the atelectasis is the absorption 
of the air. The failure of the blood to be aerated leads to stagna- 
tion — a condition which predisposes to catarrhal pneumonia ; since it 
renders the part a favorable nidus for micro-organisms. 

(b) Chronic obstruction occurs in chronic affections of the bron- 
chial tubes from cicatricial contraction ; also from the presence of a 
foreign body, or from pressure from the outside, as by an aneurysm. 
The consequences are (i) obliteration of the air- vesicles, the part of 
the lung supplied by the bronchus being converted into a scar ; (2) 
gangrene; (3) ulceration, the character depending on the micro- 
organisms present. If the tubercle bacillus is present, it sets up its 
special lesions. (4) Dilatation. 

Dilatation or Bronchiectasis may be (a) sacular or (J?) 
cylindrical. Two factors are necessary for the production of dilata- 
tion : (1) a weakening of the tube, and (2) a distending force. The 
weakening of the walls is generally due to chronic inflammations, 
particularly those accompanied by atrophic changes. If it is uni- 
form, the dilatation will be cylindrical. Such dilatations are most 
common in the lower lobes, and affect especially the larger bronchi. 
The distending force is nearly always inspiratory, and acts upon 
the part of the bronchus between the obstruction and the trachea. 
The resistance to the entrance of the air may be constituted by an 
obstructing body, or there may be an area of atelectasis. Accord- 
ing to some authors, the distending force is expiratory, the dilata- 
tion occurring behind the obstructing body, which is supposed, in 
such cases, to have a valve-like action, allowing the entrance but 
not the escape of the air. Saccular dilatation affects chiefly the 
bronchial tubes of the middle parts of the lung, and is due to a 
localized weakening in the walls of the tubes, usually brought about 



THE LUNG. 207 

by tuberculous changes. The distending force does not play a 
prominent role in this form of bronchiectasis, which we may com- 
pare to a false saccular aneurysm. 

Dilatation may also occur in connection with chronic fibroid 
peribronchitis, the contraction of fibrous bonds extending inward 
from the pleura exerting traction on the bronchial tubes. 

Effects. From their close proximity to the external air, the 
fluids in the bronchial tubes readily decompose, and may set up 
ulceration or gangrene. 

THE LUNG. 

Anatomy. This has in part been described under Bronchial 
Tubes. The bronchi branch dichotomously until they terminate in 
pouches, known as infundibula, from which spring the air-vesicles. 
The terminal bronchioles, which lead into the infundibula, are 
called air-passages and each of them communicates with from 3 to 5 
infundibula, which together constitute an acinus. From 9 to 12 
acini constitute a lobule, which is supplied by a single bronchial 
tube, and represents the macroscopic unit of the lung. The air 
vesicles are lined by flat epithelium, resembling both in its appear- 
ance and in its behavior under pathologic conditions, the endothe- 
lium. In the walls of the vesicles we find an abundant capillary 
network, held together by connective tissue containing many elastic 
fibers. The blood-vessels are only separated from the air in the 
alveoli by the flat endothelial cells, and are exposed to the air on 
two sides. 

Malformations. — There may be absence of a part or the 
whole of one lung, a condition generally accompanied by a defect 
in the diaphragm and the presence in the thoracic cavity of some 
of the abdominal viscera. 

Circulatory Disturbances, (a) Active Hyperemia. — 
This may be due (1) to active exercise. (2) It may occur acutely 
after exposure to cold. The origin of this variety is obscure, but by 
some the condition is considered a form of pneumonia. In many 
cases the pneumococcus is present, but evidences of inflammation 
are wanting. A fatal termination may occur, the lung at autopsy 
being swollen, red, and edematous, and oozing a frothy, blood- 
stained serum on section. (3) Active hyperemia is best marked in 
the beginning of croupous pneumonia. (4) Active congestion may 
be caused by brain lesions, as of the pons and medulla, more rarely 



2o8 NOTES ON PATHOLOGY. 

of the cortex. In the latter case the hyperemia is in the lung of the 
opposite side ; when due to lesions of the pons and medulla, it is 
irregularly distributed on both sides. (5) Embolic hyperemia. The 
congestion due to the lodgment of an embolus may not go on to 
hemorhagic infarction, but may remain as congestion until relieved. 
(b) Passive Hyperemia.— (1) Hypostatic congestion affects 
the dependent parts of the lung, and occurs in the preagonic period 
and in the low stages of acute infectious diseases. It is due to fail- 
ure of the heart's action, to loss of vascular tonus, and to impaired 
respiration, so that the blood is but poorly aerated. 

(2) Atelectatic hyperemia is brought about by obstruction of a 
bronchus, and occurs in the area beyond the obstruction. The 
blood in this area becomes surcharged with carbon dioxid, and does 
not readily flow out of the part. 

(3) Congestion from valvular heart disease of either the left or 
the right side of the heart. 

Appearance of congestion. It is often difficult to distinguish 
between active and passive congestion. In the former the lung is 
usually dark-red, swollen, and denser, and at times edematous, at 
others dry. In passive congestion the organ is bluish or purplish in 
color, and there is usually a well-marked edema, so that fluid oozes 
from the cut surface. 

Edema is a condition in which the lung is enlarged and the air- 
vesicles and interstitial tissue are infiltrated with serum. On 
pressure the cut surface of the lung exudes an abundant frothy 
fluid. Edema is not always associated with hyperemia — in some 
cases the lung is anemic. That which accompanies hyperemia is 
readily accounted for on mechanical grounds, but that found in an 
anemic lung is more difficult of explanation. There is probably 
some alteration in the vessel walls, permitting the passing out of a 
clear fluid. 

Hypostasis always plays an important part in all forms ot 
passive congestion. 

Results of passive congestion. (1) If long continued it leads to 
cyanotic induration of the lung, an overgrowth of connective tissue, 
with a deposit of pigment. (2) Edema. (3) Splenization or hypo- 
static pneumonia. This is a more acute change At first there is 
an exudation of serum — an edema ; after 2 or 3 days the epithelial 
cells of the air vessels become loosened, and some proliferation of 
these cells takes place. This gives rise to consolidation, the affected 



THE LUNG. 209 

part, especially the base of the lung-, being solid and airless, but 
oozing a considerable amount of blood on section. This condition 
of gradual consolidation is called splenization or hypostatic pneu- 
monia, the latter term being used for a more acute process of con- 
solidation, but there is no other difference between the two. The 
consolidated area is dark-purplish in color, the surface of section is 
smooth and shining, and small pieces sink in water. On pressure a 
large quantity of bloody fluid, unmixed with air, oozes from the 
surface ; in true pneumonia such a fluid cannot be squeezed out. 
Hypostatic pneumonia is very common — it is seen in nearly all fatal 
cases of acute infectious diseases. 

Hemorrhages may be minute or extensive. To the latter 
the name of " pulmonary apoplexy '\ is given. Blood may be 
found in the lung when the hemorrhage occurred higher up, as 
from rupture of an aneurysm into the trachea or a bronchus. 

Causes of hemorrhage. (1) Hemorrhage may result from the 
various hyperemias. (2) Central disease, especially sudden lesions 
of the pons. These hemorrhages may be circumscribed and retained 
within the pulmonary tissue. (3) Traumatism. (4) Tuberculosis. 
(a) Hemorrhages in tuberculosis are most frequent from the walls 
of cavities, the bleeding occurring either from vessels eroded by the 
tuberculous process, or from the rupture of small aneurysms. (U) 
In some instances the hemorrhage occurs very early in the disease, 
before any cavities have formed. The bleeding in such cases is due to 
ulceration of the bronchial walls with involvement of the bronchial 
vessels. This form of hemorrhage was formerly believed to be the 
cause of the tuberculosis in the lung, and to a certain extent this 
view is correct. The process is often rapid after the hemoptysis, 
the hemorrhage having made the pulmonary tissues a favorable 
soil for the growth of the tubercle bacilli; beside this, the blood 
may carry the organisms to other parts of the lung. (5) Vicarious 
hemorrhage may be due to suppression of the menses or, more 
rarely, to an arrest of the bleeding from hemorrhoids. (6) Ob- 
struction in the blood-vessels, i. e., hemorrhagic infarction, from 
embolism and thrombosis. This is most frequent on the right 
side, although the difference between the two sides is not great. 
The infarct is pyramidal in shape, with the base toward the 
pleura, and the apex toward the root of the lung. It is dark- 
red in color, elevated, and on section is shining, but less so than is 
the lung in edema. The tendency is to absorption, the degenerated 

13 



210 NOTES ON PATHOLOGY. 

tissue being replaced by a scar, which is usually situated at the base 
or in the middle lobe ; scars at the apices are generally of tuber- 
culous origin. If the embolus is specific, an abscess results. 

Inflammation of the Lung, Pneumonitis, or Pneu- 
monia, is of several varieties, as follows: (i) Fibrinous, 
croupous, or lobar. (2) Catarrhal, or lobular. (3) Desquamative, 
or caseous. (4) Purulent. (5) Interstitial, productive, or fibrous. 

Fibrinous, Croupous, or Lobar Pneumonia, is a true 
inflammation of the air vesicles, characterized by proliferation of the 
cells, by exudation, and by a coagulation necrosis of the exudate. 
The epithelial cells of the alveoli in their pathologic behavior 
are comparable to the cells of the intima of blood-vessels, or those 
lining the opposing surfaces of a serous membrane. The process 
of inflammation is divisible into three stages : 

(a) Stage of engorgement or congestion. The capillaries of the 
intervesicular walls are enormously distended, and bulge into the air 
vesicles ; the lung tissue is in a condition of inflammatory edema, the 
air vesicles being filled with a serous fluid, some red cells, and 
loosened endothelial cells from the lining of the alveoli. These 
cells as well as those in the walls of the vesicle, show evidences ot 
proliferation. The exudate soon undergoes coagulation necrosis, 
giving rise to the second stage, that of consolidation. 

(b) Stage of Consolidation. This may be divided into two sub- 
stages : (o) Stage of red hepatization, and (P) stage of gray hepati- 
zation. 

(a) Stage of red hepatization. The air vesicles are now filled 
with fibrin holding in its meshes red corpuscles and endothelial 
cells. In some vesicles almost none but red cells are found ; in 
others, both red corpuscles and endothelial cells are present, the 
latter disposed along the walls of the vesicles. 

The affected lobe is enlarged and does not collapse on opening 
the chest ; it is heavy and solid, and sinks in water ; it is dark in 
color and fragile, being easily broken with the finger. The surface 
of section is dry and granular from the projection of plugs of fibrin 
from the air vesicles. The pleura over the pneumonic area is also 
inflamed, whence the name " pleuro-pneumonia." In some cases 
the pleural changes are slight, the membrane being only dry and 
sticky ; in others the inflammation is of the same nature as that 
of the lung, being characterized by an exudation of fibrin. 




LOBAR PNEUMONIA. ail 

(0) Stage of gray hepatization. The change from red to gray 
hepatization is a gradual one, and is due to the increased outwander- 
ing of leukocytes, the destruction and ab- 
sorption of the red cells, and the anemia of 
the lung produced by pressure of the exu- 
date upon the vessels. The color of the 
lung is gray, and the section is granular, 
resembling, especially on fracture, broken 
granite. This granitic appearance is par- 
ticularly marked in the lung of adults ; in 
children the color is more uniform and 
somewhat yellowish. 

(c) Stage of resolution. As the process continues, the exudate 
begins to undergo fatty degeneration, mucoid change (the epithe- 
lium), and liquefaction. The degenerated material is emulsified 
by the exudation of a fluid, and is in part absorbed by the lym- 
phatics and blood-vessels, in part is expectorated. The lung on 
section is smooth, and on pressure exudes a pus-like fluid, which, 
however, is not pus, but a fatty emulsion. Toward the end of the 
stage of resolution the color of the lung becomes again red, the 
blood-vessels being released from pressure by the removal of the 
exudate. 

Terminations. 1. Resolution is the most frequent. 2. Abscess. 
This is a rare termination, and is usually due to mixed infection, 
generally by the pneumococcus and pyogenic organisms, sometimes 
to the pneumococcus alone. The abscess is large, and is apt to in- 
volve the whole lobe, and eventually ruptures into the pleural 
cavity, or into a bronchus. Cicatrization may then take place. 
3. Gangrene. The disturbances of the circulation in the pneu- 
monic portion of lung may predispose to gangrene, or there 
may be an infection with some special micro-organism. 4. Fibrous 
change. The changes in this are the same as occur in regeneration 
anywhere. The cells of the air vesicles proliferate and push into 
the fibrin meshwork ; new blood-vessels form, and, finally, there is 
organization and the development of fibrous connective tissue. A 
lung so affected is termed " carnified," an adjective also applied to 
a compressed lung. This termination is rare, and seems to occur 
in such cases in which there has previously been a tendency to the 
formation of fibrous tissue — a fibrous peribronchitis. 



212 NOTES ON PATHOLOGY. 

Seats. In the majority of cases lobar pneumonia affects one 
lower lobe, usually the right. Limitation to one apex is rare. 
At times different portions of the lung present different stages of 
pneumonia, the lower lobe being generally most advanced. A 
pneumonia which travels from one lobe to another is termed 
"wandering pneumonia." 

Etiology. The cause of pneumonia, in at least 90 per-cent of 
all cases, is the pneumococcus or diplococcus of Frankel. It does 
not occur in the normal lung, but in pneumonia is found in the 
exudate in the air vesicles, both within and between the cells, and 
in the vesicular walls, and also in the sputum. 

It is normally found in the saliva of certain persons, and was 
discovered there by Sternberg. In reality it is not a coccus but a 
lanceolate bacillus, with pointed ends, occurring in twos, fours, or 
in chains. In the human body, but not in cultures, the organism is 
surrounded by a capsule, which is best demonstrated by the follow- 
ing method. The prepared cover glass is treated with a 1 per-cent. 
solution of acetic acid, washed in water, and stained — perhaps best 
with fuchsin. The pneumococcus also stains by Gram's and by 
Weigert's method. Its property of taking the stain by Gram's 
method distinguishes it from an organism somewhat similar in 
appearance, at times found in pneumonia, the bacillus of Fried- 
lander, which is not stained by Gram's method. 

Cultivation is difficult, and cultures present nothing character- 
istic on any medium. The organism soon loses its virulence when 
grown artificially. 

That the pneumococcus is the cause of pneumonia has been 
proved by experiment on the lower animals. These are very sus- 
ceptible, and when inoculated with a fully virulent culture die of 
septicemia in 24 to 48 hours, the micro-organisms being present in 
the blood. If the virulence is reduced — and this is readily accom- 
plished by successive cultivations or by cultivation at a temperature 
of 41 ° or 42 C. — pneumonia can be produced in animals by 
inhalation. 

The organism in its development elaborates certain poisons. At 
the same time the system manufactures an antitoxin, and it has been 
found that the serum of convalescent patients is capable of immuniz- 
ing animals. With regard to man the results have not been positive. 

The pneumococcus is also found in certain cases of pleurisy, 
meningitis,, middle-ear disease, endocarditis, ana disease of joints. 



CATARRHAL, OR LOBULAR PNEUMONIA. 



"3 



Normally, it occurs, as has been stated, in the saliva, and also in the 
mucus of the nose and throat. It seems that predisposing causes 
are necessary to render it virulent — of these causes cold appears 
to be one. 

Pneumonia may at times be contagious, and epidemics have 
occurred in hospitals, prisons, and barracks. In such cases there is 
often a mixed infection of the pneumococcus and the streptococcus. 
Clinically, these epidemic pneumonias seem to be connected with 
erysipelas (Guiteras). 



Catarrhal, or Lobular Pneumonia is characterized by 
an exudate in the air vesicles consisting of fluid, red and white 
corpuscles, and epithelial cells. The exudate has no marked 
tendency to coagulation necrosis, though there may be a few threads 
of fibrin. The fluid can be demonstrated by plunging the lung into 
boiling water, when it is coagulated. 

Macroscopy. Catarrhal pneumonia is a lobular process ; rarely, 
from the confluence of neighboring lobules, a whole lobe may be 
involved, but in such a case the affected lobules present different 
stages, and the consolidated area is not uniform as in croupous 
pneumonia. The inflamed lobules are plainly visible, particularly 

under the pleura; they are gener- 
ally pale and surrounded by con- 
gested but healthy lung tissue. 
At times, especially in the early 
stages, the affected areas are dark 
from congestion. 

On section, the s u r f a c e is 
smooth, i. e. y not granular as in 
croupous pneumonia; the lobules 
stand out prominently, are firm and 
of the size of hazel-nuts or larger. 
The center of the lobules is usually 
paler than the periphery. The surface of section is moister than in 
croupous pneumonia and on pressure exudes a frothy serum from 
the healthy portions, and a thicker, grayish-yellow fluid, from the 
diseased areas. 

Etiology. The disease is micro-organismal in origin, being in 
some instances due to the pneumococcus, especially in the young 
and old, in othe.^ to mixed infection, while certain forms are caused 




«4 NOTES ON PATHOLOGY. 

by the streptococcus or the staphylococcus alone. Pure cultures 
of the pneumococcus are rarely found. 

Three varieties of catarrhal pneumonia are distinguished as to 
their etiology, although they are not different anatomically. 

1. A bronchial form. The pneumonia is the result (a) of direct 
extension of a bronchitis or peribronchitis, or (b) of the aspiration 
of irritant particles which act mechanically as emboli, setting up 
atelectasis and subsequently pneumonia {atelectatic pneumonia), or 
as direct irritants to the air-vesicles, or as specific emboli, when con- 
taining micro-organisms. The first variety is common in children, 
occurring frequently in the course of measles, diphtheria, and 
whooping-cough ; it is, indeed, present in nearly all fatal cases ot 
these diseases. 

2. A hypostatic form. Hypostatic pneumonia is due to the 
infection, probably by aspiration, of areas the seat of intense hypo- 
static congestion. It occurs in low fevers and in the preagonic 
period, states in which there is a tendency to the aspiration of 
irritant materials, which from a paralytic condition of the bronchi 
are not coughed up. Section of the pneumogastric nerves in 
animals leads to the same form of pneumonia by inducing a similar 
paralytic state of the air-passages, which favors aspiration. 

Terminations. Catarrhal pneumonia has a marked tendency 
to recovery, nevertheless there is a general belief that it is a very- 
fatal disease. This arises from the fact that it is so often combined 
with grave affections like tuberculosis, diphtheria, measles, and 
whooping-cough, in which the superaddition of the catarrhal pneu- 
monia to the original disease is apt to prove fatal. Another cause 
of the misconception is the confounding of caseous with catarrhal 
pneumonia. Catarrhal pneumonia is a benign process, tending to 
early fatty degeneration and removal of the exudate, and reso- 
lution. 

Rarely, it terminates unfavorably, in abscess or gangrene. 

Purulent Pneumonia is of several varieties. 

(a) The suppuration may be diffuse, affecting the walls of the 
air-vesicles — purulent catarrh, (b) There may be a true abscess ot 
the lung. The single large abscess usually involves an entire lobe, 
is oval or spindle-shaped, the long axis being transverse, running 
in the direction of the bronchi and blood-vessels, (c) There may 
be a purulent lymphangitis and perilymphangitis. 



DESQUAMATIVE, OR CASEOUS PNEUMONIA. 215 

Causes. (1) Aspiration of material containing pyogenic organ- 
isms, from suppurative processes in the upper air-passages, as in 
diphtheria ; or the inspiration of infected matters from without, as 
in the pneumonia of the new-born. The abscesses are usually- 
multiple and circumscribed. (2) Metastatic abscesses. These are 
small and multiple, and are secondary to suppuration elsewhere, as 
in the abdominal cavity. (3) Extension from neighboring organs 
— the mediastinum, the pleura — the suppuration traveling along the 
lymphatic vessels. (4) Extension of a suppurative bronchitis ; or 
of suppurative peribronchitis from the hilum of the lung. This 
gives rise to multiple small abscesses. (5) Abscess following lobar 
pneumonia. This is single, large, and usually involves the lower 
lobe. (6) Traumatism. (7) Rupture of a liver abscess through 
the diaphragm into the lung. 

Desquamative, or Caseous Pneumonia resembles 
catarrhal pneumonia in appearance, but while the latter is acute 
and tends to recover, caseous pneumonia is a subacute or chronic 
process, tuberculous in nature, and goes on to destructive ulceration 
and cavity formation. 

The process is characterized by a congestion of localized areas, 
followed by an exudation of an albuminous fluid, and a desquama- 
tion of the epithelial cells, and a proliferation of these cells and 
of the connective tissue cells of the intervesicular septa. The 
entire exudate, fluid and cells, subsequently undergoes a coagula- 
tion necrosis, which, however, is not a fibrin formation. 

Macroscopy. The process is confined to lobules, several oi 
these being usually involved together. They appear as pyramidal, 
grayish, translucent nodules, elevated, and harder than the sur- 
rounding tissues, and communicate with a bronchus, which is also 
involved, hence the term caseous broncho-pneumonia. The bron- 
chus is always prominent on section. 

The extent of the area affected varies from a single lobule to 
the involvement of an entire lobe — lobar caseous pneumonia — 
brought about by the running together of neighboring lobules. 
The appearance of this lobar form differs from that of croupous 
pneumonia, in that it presents a distinctly mottled appearance due 
to the lobules being in different stages of inflammation. 

Microscopy. There is a marked proliferation and desquamation 
of the epithelial cells of the air-vesicles, together with a proliferation 



216 



NOTES ON PATHOLOGY. 




of the connective tissue cells of the septa and of the blood-vessels. 
The air-vesicles become filled with cells which press upon the 
blood-vessels and exclude congestion. The defective blood supply 

leads to necrosis, but is not the sole 
cause, a very important factor being 
the tubercle bacillus, since caseous 
pneumonia is nearly always tuber- 
culous. 

The coagulation necrosis is fol- 
lowed by fatty and cheesy changes. 
The necrosis gives rise to a disap- 
pearance of the nuclei, and also ob- 
literates the boundary lines between 
the air-vesicles. The blood-vessels are obstructed by arteritis, 
presenting a proliferation and degeneration of their endothelial cells. 
Etiology. The cause of caseous pneumonia is the tubercle 
bacillus. 

Terminations, (a) If the involved area is large, and mixed 
infection takes place, a rapid suppurative softening will follow — a 
condition termed acute phthisis, galloping consumption, or phthisis 
florida. The suppuration affects first the periphery of the involved 
lobules and produces a large number of minute cavities which give 
rise to pyemic symptoms, (b) A more frequent termination is the 
coalescence of the lobules and a slow softening, with the formation 
of cavities of larger size than are seen in phthisis florida. (c) 
Fibrous change — the formation of a capsule around the caseous 
mass which subsequently becomes calcified, (d) Resolution may 
occur, but it is difficult to say to what extent. When the involved 
area is large and there are tubercles elsewhere in the lung, the 
tendency is undoubtedly to softening. Yet it is probable that 
small areas, embracing two or three lobules, may get well. We 
must suppose this from the frequency with which small patches ot 
caseous pneumonia are seen on the autopsy table. If destructive 
phthisis followed in every case, the death-rate from pulmonary 
tuberculosis would be much greater than it is. The frequent 
presence of caseous areas also shows how common infection with 
the tubercle bacillus is, especially in hospitals. 

It is sometimes difficult to distinguish between groups of 
miliary tubercles and lobules of caseous pneumonia, but the 
diagnosis can generally be made (a) by finding in the latter the 



TUBERCULOSIS. 217 

involvement of the bronchial tube, the minute opening of which 
can be seen with a magnifying lens; (b) by the distribution of 
the lesions — miliary tubercles being scattered irregularly, while 
nodules of caseous pneumonia radiate from a bronchus as a com- 
mon center ; (c) by the fact that on pressure on a caseous lobule 
particles of cheesy material can be squeezed from the bronchial 
tube. Both forms of tuberculosis often occur together, and the one 
may be the starting-point of the other. 

Fibrous, Interstitial, Productive, or Indurative 
Pneumonia is one in which the cellular proliferation becomes 
permanent connective tissue. In time this contracts and gives to the 
lung a puckered appearance. Nearly all cases show a marked par- 
ticipation of the peribronchial tissues. Several forms are described : 

(a) A parenchymatous form, one in which the air-vesicles are 
primarily affected, and which may be due (a) to the inhalation ot 
irritant particles, as dust (pneumonokoniosis) ; (£) it may be a termi- 
nation of lobar pneumonia ; (7) it may be due to congenital syphilis 
(fibroid or white pneumonia). 

ifi) Those forms in which the air-vesicles are secondarily in- 
volved, and which are due (a) to extension of the fibroid process 
from the pleura, in cases of chronic fibroid pleurisy ; (0) to exten- 
sion along the peribronchial tissues or blood-vessels, beginning at 
the root of the lung, and extending outward in a radiating manner 
— this form may be due to syphilis ; (y) to the healing of gummata ; 
( ) to the healing of tuberculosis ; and («) to the healing of wounds. 

Tuberculosis gains access to the lung in one of three ways : 
id) by the blood, (b) by the lymph, or (c) by inhalation. 

(a) Hematogenous tuberculosis is a secondary process, the bacilli 
being brought from a primary focus, as the lymphatic glands or the 
bronchial tubes. It gives rise to miliary tubercles, the specific lesion 
of tuberculosis. The distribution may be local in the lung, affecting 
a lobe, or general, affecting both lungs. In the latter case the 
patient is apt to die of toxemia before secondary changes can occur. 
The lung in acute miliary tuberculosis is intensely congested, and 
also presents an acute bronchitis, particularly of the smaller tubes. 
The tubercles are small, grayish, translucent, and not readily seen 
unless examined by oblique light. 

(b) Lymphatic exte?ision is very common, and is secondary to 
disease of neighboring organs, as the lymphatic glands of the neck, 



ai8 NOTES ON PATHOLOGY. 

the mediastinum, and the throat ; also to tuberculosis of the pleura. 
The lesion produced is the miliary tubercle. The infection may 
travel forward to the lymphatic glands, or backward into the 
lungs. 

(c) Inhalation is the most frequent mode of infection of the 
lung, a fact proved both by animal experiments (causing animals to 
inhale dust laden with tubercle bacilli) and by clinical observation. 
The bacilli, when inhaled, lodge in the larger or smaller bronchi ; 
in the former they set up a caseous bronchitis ; in the latter they are 
apt to cause obstruction with the production of nodules of caseous 
broncho- pneumonia. From these primary lesions the surrounding 
lung tissue may become involved (a) by extension by continuity, the 
tubercle bacilli being carried by leukocytes and wandering connect 
tive tissue cells; (4) by extension along the lymphatic vessels, 
either forward or backward; (y) by extension along the blood- 
vessels with the blood ; («) by inhalation — -which may consist in the 
aspiration of blood containing bacilli, or of the material from a 
broken-down tuberculous ulcer. 

These different modes of infection may give rise to miliary 
tuberculosis or to caseous processes — the former resulting from 
extension, the latter from aspiration. It matters not which process 
is first ; caseous pneumonia may give rise to miliary tuberculosis, and 
vice versa. In chronic cases all types of lesions are usually present, 
though one as a rule preponderates. 

All lesions have a tendency to spread and to degenerate. First, 
there is a coagulation necrosis ; later, fatty and cheesy changes ; and 
finally, liquefaction necrosis. As the lung tissue contributes to the 
cellular accumulation, it also participates in the destructive changes ; 
hence the formation of cavities. Cavities vary in size and number, 
are most frequent in the upper lobes, and generally communicate 
with bronchial tubes. The walls may be the seat of caseation and 
softening, these processes contributing to the contents of the cavity, 
and also causing it to increase in size. In other cases there is a 
tendency to the formation of fibrous tissue, by which the spread of 
the tuberculous process is limited. 

Tuberculous lesions may heal, being replaced by a cicatrix ; at 
times the cheesy material becomes calcified and encapsulated. 
But these apparently healed lesions always constitute a source of 
danger ; though they may be quiescent for a time, the tubjercle 
bacilli or their spores remain active. 



TUBERCULOSIS. 219 

Inhalation tuberculosis begins most often at the apex of the 
lung, although it is probable that the bacilli find their way to the 
middle and lower lobes as frequently as to the apices, but do not 
succeed in developing. The circulation of air is less active in the 
apices than elsewhere, which may explain the more frequent locali- 
zation in them. Lymphatic and hematogenous infection may begin 
at the center of the lung. 

Mixed infection is common in tuberculosis, and leads to other 
forms of pneumonia. The pyogenic bacteria are very commonly 
present and not only cause suppuration, but frequently produce 
catarrhal pneumonia. Croupous pneumonia, especially when epi- 
demic, may complicate tuberculosis. The mixed infection may cause 
toxemia or pyemia. 

The tubercle bacillus alone is capable of producing suppura- 
tion ; the dead bacilli have been shown to be actively chemotactic. 
The toxins of tuberculosis — tuberculin — produce cachexia; the 
sudden injection causes fever and local congestion about the tuber- 
culous areas. In this congestion lies the explanation of the tendency 
of tuberculous lesions to spread, and also the danger connected 
with the use of tuberculin. On the other hand, the hyperemia is 
also a favorable condition, since it may become the basis of a heal- 
ing process. Patients suffering from tuberculosis are constantly 
absorbing tuberculin produced within them, and the same processes 
follow as after the artificial injection. 

The effect of the tuberculous process on the blood-vessels. The 
large vessels are quite resistant, and may be seen in the walls ot 
cavities or running across them. In the smaller vessels the tuber- 
culous process gives rise to miliary aneurysms, the rupture of which 
leads to hemorrhage, or to ulceration and rupture without the 
previous formation of aneurysm. 

Changes in the pleura. The pleura is the seat of changes 
similar to those of the lung, viz., either miliary or caseous tuber- 
culosis. Tuberculosis may be primary in the pleura, and may be 
miliary or caseous. At times it takes the form of a miliary tuber- 
culosis associated with pleuritis ; the pleura is greatly thickened, 
and there is a large amount of fluid, but the miliary tubercles are 
scattered and not readily seen. 

Pneumothorax or pyopneumothorax may result from the 
breaking down of a tuberculous focus in the lung. 



220 NOTES ON PATHOLOGY. 

Syphilis. — As a demonstrable lesion, syphilis is rare in the 
lung of the adult, but is quite common in children, particularly as 
a manifestation of congenital syphilis. Two kinds of lesions are 
met — (a) the gumma, which is usually multiple, and either sub- 
pleural or mediastinal (the gummy tumor is also the lesion of 
syphilis in the adult lung) ; (b) syphilitic pneumonia. This may 
originate in utero and interfere with the development of the lung. 
Histologically, there is an overgrowth of connective tissue in the 
walls of the air-vesicles ; when this is associated with fatty degen- 
eration of the epithelium, the so-called " white pneumonia " is pro- 
duced. The lung is solid, and if the condition is of intrauterine 
origin, it does not expand after birth, being in a state of " carnifi- 
cation." A more frequent cause of carnification is, however, pres- 
sure by a pleural effusion. 

Actinomycosis and Glanders.— Of internal viscera, the 
lung is one of the most frequent seats of these diseases. 

Emphysema signifies an excess of air in the lung. It is of 
two kinds, (a) acute and (S) chronic. 

(a) Acute emphysema is either vesicular or interstitial. 

i. Acute vesicular emphysema is simply a dilatation of the air- 
vesicles. Its causes are (i) obstruction of the bronchial tubes, the 
obstructing body having a valve-like action which permits the 
entrance but not the exit of air, the consequence being a mechanical 
distention of the air-vesicles. (2) Collapse or atelectasis of parts of 
the lung, producing a compensatory or vicarious dilatation in 
neighboring parts. 

The condition is transient as a rule, and the lung returns to 
normal ; in some cases pneumonia, gangrene, etc., follow, but not as 
the result of the emphysema. 

Appearance of the lung. The areas are pale, rose-colored, 2 to 
3 cm. in diameter, and surrounded by congested lung tissue. To a 
certain extent they resemble areas of catarrhal pneumonia, but 
when incised they collapse at once. The middle lobe and anterior 
borders are the most frequent seats. 

The clinical causes are different forms of bronchitis, especially 
those associated with violent cough, as whooping-cough. 

2. Interstitial emphysema is similar to subcutaneous emphysema 
In a general way it is always due to traumatism, either internal or 
external, causing a rupture of the air-vesicles. 



EMPHYSEMA. 221 

Appearance. The outline of the area is irregular, the emphy- 
sema not being circumscribed to the air-vesicles. The characteristic 
'■feature is that the air can be pushed from place to place. As a rule 
interstitial emphysema is transitory. By extending along the septa, 
the air usually reaches the subpleural space, and in some cases 
causes serious results by pressing on the lung. It may travel along 
the bronchi to the mediastinum and press upon the structures there, 
or along the fascia to the neck and even throughout the body. In 
such cases septicemia and pyemia sometimes follow. 

. (b) Chronic emphysema, or substantial emphysema. This is a 
vesicular emphysema, and affects especially the anterior borders of 
the upper lobes. The lungs are enlarged and meet in front, cover- 
ing the heart; the outlines are irregular from the projection of large 
bullae. The affected areas are pale, and seem to contain a large 
amount of coal-dust ; but the increase is only apparent, and is due 
to the striking contrast between the pale lung and the pigment. 
The bullae vary in size, and may correspond to single or to several 
lobules that have joined. The air-passages and minute bronchial 
tubes are also dilated, even before the air-vesicles are affected. 

Microscopy. The disease is characterized by an atrophy of the 
pulmonary tissue, involving the septa between the air-vesicles, and 
even between the infundibula. The tissues undergo a slow, fatty 
degeneration, and are gradually removed ; the blood-vessels take 
part in the degeneration. 

Secondary effects. The enlarged lung presses on the surround- 
ing structures, compressing the heart and displacing the abdominal 
viscera downward. Very important are the circulatory disturbances. 
The right heart, having to force the blood through a diminished area, 
becomes hypertrophied ; the pulmonary artery also enlarges, at 
times reaching the thickness of the aorta. As a result of the dis- 
turbance in the pulmonary circulation, venous engorgement 
develops, which, together with the diminution in breathing area, 
gives rise to dyspnea. 

Etiology. Two factors are concerned in the production of 
emphysema — an impaired resistance and a dilating force. The 
impaired resistance of the pulmonary tissue may be inherited or 
acquired. Acquired lessened resistance depends usually upon 
inflammatory changes — chronic bronchitis — impairing the elasticity 
of the lung. The dilating force is, as a rule, expiratory. During 
expiration the air is forced into those parts that are least protected 



222 NOTES ON PATHOLOGY. 

by the chest wall, viz., the anterior borders, the apices, and the dia- 
phragmatic wedges. 

' Senile, or atrophic emphysema is similar to the preceding form» 
There is also an atrophy of pulmonary tissue ; but as there is no 
dilating force, there is no stretching. The lung is not enlarged ; 
there are no bullae. In advanced age there is always a tendency 
to this condition, but it produces no symptoms, since the individual 
at that time of life requires less breathing space. 

Tumors. — Primary tumors of the lung are rare. Chondroma 
is more frequent than in other viscera. All other connective tissue 
tumors may occur, especially fibroma. Primary cancer is very rare, 
but sometimes springs from the bronchial tubes (the mucous 
glands). Secondary sarcoma and secondary carcinoma are quite 
common, the former more so than the latter. Cancer is most often 
secondary to cancer of the liver ; in such cases the hepatic veins 
are always found involved. Chondroma of the lung is frequently 
secondary to chondroma of other parts. 

THE PLEURA. 

The pleura is a serous membrane, and is subject to the same 
processes as other membranes of this class. 

(a) Passive congestion, with a tendency to dropsy — hydrothorax 
— -is seen in heart disease, Bright's disease, etc. Both cavities may 
be filled with fluid, but usually one contains more than the other. 
If the hydrothorax persists for a length of time, changes are pro- 
duced in the pleural membrane ; it becomes thickened, both from 
condensation by pressure and from hyperplasia of the connective 
tissue. 

(b) Hemothorax is due to traumatism or to the spontaneous 
rupture of a blood-vessel, as an aneurysm of the thoracic aorta. If 
the hemorrhage is not fatal, the blood is rapidly absorbed. 

(c) Pneumothorax. The presence of air in the pleural sac is 
due to external trauma or to rupture of the lung, the latter being, 
in turn, caused by rupture of the pleura in interstitial emphysema 
or by ulcerative processes of the lung — tuberculosis, abscess, gan- 
grene. When the rupture is due to ulceration, pyopneumothorax is 
apt to develop. 

(d) Inflammation — pleuritis, pleurisy — is serous, sero-fibrinous, 
fibrinous, or purulent. The appearances are the same as in peri- 
carditis. In fibrinous pleurisy there is a layer of yellowish lymph 



THE PLEURA. 223 

on both surfaces which can be readily removed, leaving the pleurae 
dry, opaque, and rough. At times, as in some forms of lobar or 
lobular pneumonia, there is very little exudate, and nothing is 
detected save that, when the lung is taken to the light, the pleura is 
found to have lost its shiny appearance. 

The sero-fibrinous is the form commonly described as acute 
pleurisy. It is characterized by the exudation of considerable 
fibrin and a large quantity of an opaque, pale-yellow fluid, contain- 
ing flakes of lymph and tending to coagulate. 

In serous pleurisy there is little fibrin, but a large amount 
of fluid. This form is generally subacute or chronic, and is fre- 
quently tuberculous in origin. 

Fibrinous pleurisy is apt to terminate in adhesions between the 
two layers and the obliteration, partial or complete, of the pleural 
sac. The terminations of pleurisy in general are: (1) Absorption 
of the exudate, with the formation of a few light adhesions ; (2) 
extensive adhesions ; (3) suppuration — pyothorax, empyema. 

Etiology of pleurisy. (1) Simple idiopathic pleurisy, which 
was formerly attributed to cold, but which is undoubtedly micro- 
organismal. The micro-organisms are principally the pyogenic 
bacteria; next in order of frequency, the pneumococcus. The 
pyogenic organisms may set up an ordinary sero-fibrinous pleurisy, 
which may or may not terminate in empyema. (2) Traumatism; 
here it is also the pyogenic organisms which cause the pleurisy. 
(3) Extension from neighboring organs — the bones, lung, and 
abdominal viscera. (4) Rheumatism. The rheumatic pleurisy is 
probably also micro-organismal. (5) Infectious diseases, as measles, 
scarlet fever, influenza, typhoid fever. The pleurisy is usually 
caused by the pyogenic bacteria, but may be due to the specific 
organisms of the disease, as at times in influenza and typhoid 
fever. Tuberculosis may give rise to a latent, chronic, serous 
pleurisy or to. an empyema. (6) Pyemia. 

Etiology of empyema. Empyema may be (a) a termination of an 
ordinary pleurisy ; (b) it may be due to direct pyogenic infection, 
or (c) to rupture of the lung. Empyema is not rarely primarily 
tuberculous, or is secondary to tuberculosis of the bones or lym- 
phatic glands. 

Effects of pleural effusion on surrounding organs, (a) The pres- 
sure flattens the dome of the diaphragm, (b) The lung is com- 
pressed and becomes carnified. If the compression continues, the 



2*4 NOTES ON PATHOLOGY. 

connective tissue of the air-vesicles becomes hyperplastic, a true 
fibrous pneumonia being established, which leads to obliteration of 
the air-vesicles, (c) The heart is pressed upon, and also (d) the 
opposite lung. 

Tumors. Primary tumors are rare. Some cases of fibroid 
thickening have been described as diffuse fibroma ; they are on 
the border-line between inflammatory hyperplasias and tumors. 
Endothelioma is comparatively frequent as a primary growth. 
Secondary carcinoma is quite common, being secondary to cancer of 
the mammary glands. 

THE THYROID GLAND. 

Anatomy. The thyroid is a compound tubular gland consist- 
ing of two lateral lobes joined by a middle lobe, called the isthmus, 
which lies in front of the trachea ; the weight of the gland is 30 to 
60 grams. Histologically, the organ consists of numerous closed 
acini, lined by a low columnar epithelium. 

Function. The gland is held at present to subserve one of two 
functions : (a) to aid nutrition ; (b) to manufacture substances which 
act as antitoxins. The latter theory is the more reasonable one ; 
the first really is not an explanation at all. 

Malformations. Absence of the thyroid body is rare; the 
gland may be congenitally small or large. At times accessory 
thyroid glands occur, and have been found behind the trachea, 
inside the trachea, and in other places. Their existence has in 
some cases explained the non-occurrence of myxedema after extir- 
pation of the thyroid gland in monkeys. 

Circulatory Disturbances.— Graves' or Basedow's disease, 
or exophthalmic goiter. This is characterized by an active dilatation 
of the blood-vessels, with some degree of hypertrophy of the gland 
structure, due to a disturbance in the nerve centers controlling the 
circulation of the gland and the body in general. 

Inflammation. — (a) Acute thyroiditis, though called idio- 
pathic, is probably an infectious disease similar to mumps. The 
gland is greatly swollen, and causes serious pressure symptoms ; 
resolution is, however, the rule. 

(b) Suppurative thyroiditis is due to embolic processes or to 
direct infection from without. 

Chronic enlargeme?it of the thyroid gland— goiter. Anatomically, 
the enlargements are of two forms : (a) an hypertrophy with 



THE THYROID GLAND. 225 

marked tendency to degeneration ; (b) an adenoma. It is not 
always easy to separate these forms, whence arises the claim of 
some authors that all enlargements are hypertrophies, while others 
hold that they are all adenomas. We are dealing with an hyper- 
trophy when there is enlargement of the follicles with an increase 
in their number. The enlargement is either uniform (the perfect 
type of hypertrophy) or irregularly distributed, but without giving 
rise to a localized enlargement. In adenoma there is a localized 
enlargement — a tumor formation in a part of the gland. The 
follicles lose their normal outline, and have a marked tendency to 
the formation of cylinders lined by epithelial cells in which colloid 
change is taking place. Pure hypertrophy is rare. 

The majority of goiters are associated with an impairment in 
the functional activity of the gland, and show various degenerations. 
These are : 

(1) Colloid change. This is normal to a certain extent, but is 
very marked in hypertrophy, and may give rise to " cystic goiter." 
(2) Fibroid change presents itself in the forms of bands of connec- 
tive tissue, which may contract and cause atrophy of the gland 
structure. (3) Hyaline change of the walls of the blood-vessels 
and other connective tissue. It is frequently associated with colloid 
or mucoid change. (4) Cystic change, from colloid or mucoid 
degeneration. (5) Telangiectatic change. (6) Hemorrhages. (7) 
Calcareous infiltration. 

All these changes may be found in different parts of one goiter 
at the same time. 

Myxedema is a nutritional disease due to interference with, or 
loss of the function of the thyroid gland. That such is its cause 
may be inferred from the following facts : (a) myxedema develops 
frequently in goitrous persons ; (b) surgical interference with the 
thyroid gland in man, and (c) experimental removal in some animals 
have been followed by general disturbances similar to, if not identi- 
cal with myxedema. 

One of the most striking features of myxedema is a swelling 
of the subcutaneous tissue. It is a pale, translucent swelling 
resembling edema, but it does not pit, and affects especially the face 
and hands. In some cases the new material is myxomatous, but in 
the majority it does not contain mucin, but a substance that 
resembles it. 

16 



226 NOTES ON PATHOLOGY. 

Nervous disturbances are always present in myxedema, and 
are (a) a peculiar tremor affecting chiefly the upper extremities, and 
occurring especially after sudden removal of the gland ; (d) slow- 
ness of muscular movements ; (c) mental impairment, eventuating 
in idiocy, particularly in cases where the abolition of the gland 
function occurred early in life or was congenital. In the last class 
of cases the mental and trophic phenomena are most marked, 
consisting in idiocy and arrested growth of the bones (cretinism, or 
the cretenoid state). 

Myxedema is progressive, and terminates fatally. 

It is not definitely known how the changes noted in myxedema 
are brought about, but they are thought to depend on the failure of 
certain poisonous substances, which normally are neutralized by 
metabolic products of the thyroid gland, to be destroyed. This 
view is supported by the fact that the introduction of thyroid gland 
or of its juice into the body after the symptoms of myxedema have 
developed, produces relief of these symptoms. 

Etiology of goiter. Goiter is endemic in certain localities, and 
affects individuals of all ages. Its cause is supposed to be some- 
thing in the drinking water, perhaps a micro-organism. Children 
in the goiter districts often present congenital myxedema, a condi- 
tion called cretinism, or the cretinoid state. 



CHAPTER XIII. 



DISEASES OF THE KIDNEYS. 

Anatomy. The kidney is 11-12 cm. long, 5-6 cm. wide, and 
3-4 cm. thick, and weighs 150 grams, the left being from 3 to 5 
grams heavier than the right. Both kidneys hold a ratio to the 
body weight of 1 to 200, and to the heart of 1.1 to 1. 

The kidney is a compound tubular gland. Each tubule begins 
in a closed sac, the capsule of Bowman, which is invaginated and 
surrounds a tuft of blood-vessels — the glomerulus. Tracing a 
tubule from the capsule, we first have the proximal convoluted tubule, 
then a narrow straighter portion, the loop of Henle, consisting of a 



DISEASES OF THE KIDNEYS. 227 

descending and an ascending portion ; then another convoluted por- 
tion, and finally the collecting tubule. With the naked eye we can 
distinguish in the kidney a cortical and a medullary portion. The 
cortex occupies the outer third, is granular in appearance, and con- 
sists of the labyrinth and the medullary rays. The former contains 
the glomeruli and the proximal and distal convoluted tubules. The 
latter are small pyramids apposed with their bases to the bases of 
the medullary pyramids, and are composed of the primary collect- 
ing tubules. The medulla makes up two-thirds of the organ, and 
consists of from 8 to 18 striated pyramids, which contain the loops 
of Henle and their limbs, and the large collecting tubules. Pro- 
jections of the cortex extend down between the pyramids as the 
columns of Bertini. 

Character of the epithelium, (a) In the capsule, a single flat 
layer; (b) in the convoluted tubules, a granular, striated, poly- 
hedral epithelium; (c) in the descending loop of Henle, flat 
cells, with large nuclei, alternating in their position on opposite 
sides of the tubule ; (d) in the loop and ascending limb, faintly 
striated, polyhedral cells ; (e) in the collecting tubules, columnar 
epithelium. 

The renal epithelium, being highly specialized, is easily dis- 
turbed in its metabolism. The blood-vessels of the kidney divide 
into two sets — one for the cortex, and one for the medulla. 

Functions. The kidneys secrete from 1000 to 1500 c.c. of 
urine in 24 hours, containing solids to the amount of 1 gram to 
1 kilogram of body weight. The amount of urea excreted is 
30-40 grams ; of uric acid, y 2 gram. The important waste products 
excreted by the kidney are not elaborated by the organ, but are 
produced in all tissues of the body — in greatest part by the liver. 
By a process of osmosis, the kidney allows certain substances to pass 
from the blood into the urine, while it retains others. In addition, 
the renal epithelium actively takes up from the blood certain sub- 
stances and discharges them into the uriniferous tubules. When 
the epithelium is diseased, components of the blood which should 
be retained, pass out into the urine, while the excrementitious 
matters, which should be eliminated, are not removed, and, accumu- 
lating in the body, cause poisoning. 

Malformations. — One kidney may be absent or hypoplastic ; 
a more common anomaly is the horseshoe kidney, in which the 
two kidneys are joined at one end, usually the lower. 



228 NOTES ON PATHOLOGY. 

Circulatdry Disturbances. — (a) Passive congestion is usu- 
ally due to valvular heart disease and leads to the condition termed 
cyanotic kidney. The kidney is swollen, dark, and firmer than 
normal ; the blood-vessels are sclerotic, and there is a slight degree 
of interstitial inflammation, especially about the blood-vessels. 

(6) Infarction. The hemorrhagic infarct is more common than 
the anemic. 

Inflammations. — A. Parenchymatous Inflammations. i. 
Acute parenchymatous nephritis. This is an inflammation in which 
degeneration of the epithelium is a prominent feature. 

Macroscopy. The organ is enlarged, especially in thickness, 
and feels hard, the result of being swollen within a non-yielding 
capsule ; when cut open it is really softer than normal. The capsule 
strips readily, and the surface of the organ is congested, the stellate 
veins being prominently marked. On section, the kidney shows a 
diffuse redness, with punctate points in the cortex corresponding to 
the glomeruli. In some cases there is considerable hemorrhage 
into the cortical substance, giving rise to hemorrhagic nephritis. 
The swelling affects particularly the cortex, which is usually also 
paler than the pyramids, but shows prominently the medullary rays. 
The pyramids are not swollen, but are intensely congested. The 
organ presents an opaque appearance, as if it had been cooked. 

Microscopy. In mild cases, as after anesthetization, or in 
jaundice of short duration, the cells of the convoluted tubules are 
in a state of slight cloudy swelling, the normal granulation being 
intensified. In severer cases the nuclei of the cells cease to stain, 
and the cells become flayed out and break down into granules. At 
the same time an albuminous fluid is poured out, which coagulates 
in the lumen, and together with the granular material forms tube- 
casts. The broken-down cells are replaced through karyokinesis 
by new cells ; these, however, are smaller and flatter than normal; 
they may remain or may also break down. 

In very severe inflammations all parts of the kidney are 
affected ; in ordinary cases, however, it is especially the convoluted 
tubules. Some cases present chiefly involvement of the glomeruli — 
glomerulonephritis. The cause of this is not distinctly understood ; 
probably there is an antecedent circulatory disturbance. The flat 
epithelium lining the capsule of Bowman shows active hyperplasia, 
but degeneration is not marked. The tuft is also affected and is 
infiltrated with a large number of nuclei. 



DISEASES OF THE KIDNEYS. 229 

In another group of cases the collecting tubules are chiefly- 
involved, a form termed catarrhal nephritis, which is character- 
ized by desquamation of the epithelium. The cells do not show 
any great tendency to degeneration, but are discharged bodily. 
There is also some proliferation. By pressure it is possible to 
squeeze out little plugs from the ends of the tubules of the pyramids. 

The tendency of acute parenchymatous nephritis is to recovery, 
although some cases become chronic. 

Etiology. Catarrhal nephritis is usually an extension of an 
inflammatory process from the bladder, ureter, and pelvis of the 
kidney. Parenchymatous nephritis of the convoluted tubules and 
the glomeruli results from the circulation of poisons in the blood. 
These poisons are : (a) those of the acute infectious fevers — espe- 
cially, yellow fever, Asiatic cholera, diphtheria, and scarlet fever ; 
(b) poisons such as alcohol, arsenic, phosphorus, cantharides, ether, 
and chloroform ; (c) certain unknown poisons which produce the 
nephritis formerly attributed to cold. Acute Bright's disease is 
probably an infectious process, the special lesion of which is in the 
kidney. 

2. Chronic parenchymatous nephritis is due to one of two 
causes. It is the result (a) of an acute attack which does not go 
on to complete recovery, as after scarlet fever or diphtheria, or (b) 
of the continued action of irritants, such as in large doses give rise 
to acute nephritis. We know but little of the nature of these 
poisons. It has been said that their presence in the blood is due 
to faulty elimination by the kidneys, but it is probable that they 
are primarily the cause of the kidney changes. To these poisonous 
substances are then added the retained waste products. Alcohol 
used for a long time may produce the lesion, either by directly 
acting on the kidney or by affecting metabolism in such a way 
that poisons are elaborated which act on the kidney. 

Macroscopy. Very often we find the features of the acute form, 
because many cases terminate fatally from an acute exacerbation of 
the disease —this obscures the lesions of the chronic form. When 
we can distinguish, we find that the organ is pale and on section 
presents a variegated appearance, yellowish areas of fatty degenera- 
tion being surrounded by reddish zones. The typical appearance is 
the large white kidney — a large, flaccid organ, the capsule of which 
strips readily, and the surface of section of which is gray or yel- 
lowish, especially in the cortex. 



330 NOTES ON PATHOLOGY. 

Microscopy. The epithelial cells, especially those of the con- 
voluted tubules, have undergone fatty degeneration. They con- 
tain large refracting granules or even oil-drops ; these may also be 
seen in the tubules and on the tube-casts. Some of the tubules 
have lost their epithelium entirely and are shriveled up. 

The duration of the pure form of chronic parenchymatous 
nephritis is very short — a few months. When interstitial changes 
are present, the course is slower. 

It is a question not yet settled whether the changes in chronic 
parenchymatous nephritis are properly to be called inflammatory. 

B. Interstitial nephritis, i. Acute interstitial nephritis, or sup- 
puration of the kidney. Its causes are : (i) Extension of suppura- 
tion from neighboring organs — perinephritis, peritonitis, etc. (2) 
Hematogenous infection — pyemic emboli. (3) Extension of sup- 
puration from the urinary tract. 

In the hematogenous form there are multiple foci, especially in 
the cortex. That due to extension from the urinary tract affects 
primarily the pyramids, giving rise at first to a true catarrhal 
nephritis, then to abscesses of the pyramids. Eventually the whole 
kidney may be converted into a pus sac. 

This form is connected with obstruction to the outflow of the 
urine, from disease of the urethra (stricture, hypertrophied prostate), 
the bladder, ureter, or pelvis of the kidney. The urine becomes 
infected with micro-organisms which travel upward against the 
current of the urine. 

When infection does not take place, the fluid accumulates and 
distends the ureter and pelvis, causing hydronephrosis. A catarrhal 
nephritis follows, but not suppuration. Finally atrophy of the 
kidney substance takes place. Calculi are the most frequent cause 
of this condition, but they often lead to suppuration — pyelonephrosis. 

2. Chronic interstitial nephritis. (1) Circumscribed form — 
scars of the kidney. These are generally found on the surface of 
the organ and are due either to the healing of syphilitic gummata 
or to the healing of infarcts. Syphilitic scars are usually stellate 
and not as deep as embolic scars. The latter are very deep and 
may affect an entire section of the kidney, dividing the organ into 
two parts. 

It is not always possible to differentiate between the two forms 
of scars, and it is then necessary to look for other evidences of 
syphilis or for sources ol emboli. 



DISEASES OF THE KIDNEYS. 231 

(2) Diffuse interstitial nephritis appears in two forms, (a) The 
one is a later stage of chronic parenchymatous nephritis. The 
large fatty kidney undergoes atrophy, the degenerated cells are 
thrown off, and connective tissue is substituted. The organ is re- 
duced in size and its capsule adherent. ; its size may be smaller 
than that of the red contracted kidney. This is the most frequent 
form of Bright's disease. 

Under the microscope a diffuse round cell infiltration is noted ; 
many of the tubules are empty, in others the cells are preserved ; 
still others show swollen cells. This variation gives rise to a 
mottled appearance on the surface of section — yellowish islands are 
seen surrounded by congested connective tissue; the yellow color, 
however, predominates. 

(b) A primary chronic interstitial nephritis — the contracted or 
gouty kidney. The causes of this are obscure — it is due to irri- 
tants circulating in the blood ; often it is associated with arterio- 
sclerosis. Alcohol and other poisons, introduced from without or 
generated within, may produce it, especially the uric-acid group ol 
compounds. There is also an hereditary tendency to the disease in 
certain families. 

In the early stages the organ is slightly enlarged, of a reddish- 
gray color, and firmer than normal. Contraction follows, and the 
kidney eventually becomes small and indurated ; the color is red- 
dish , the surface granular, and the capsule densely adherent. Cysts 
are frequently present in the cortex from closure of the tubules — 
they are seen in both forms of interstitial nephritis. The fluid of these 
cysts may be urinous ; after the removal of the cells it is mucoid in 
nature, or it may be colloid if the cells undergo this degeneration. 

Microscopy. In the early stages we find a round cell infiltra- 
tion about the blood-vessels, the tubules, and the glomeruli. The 
blood-vessels show endarteritis and periarteritis, and become enor- 
mously thickened; the capsule of Bowman is also greatly thickened. 
The connective tissue contracts and causes atrophy of the epi- 
thelium. In both forms the epithelium shows fatty changes, but in 
that following chronic parenchymatous nephritis this degeneration 
is prominently marked, while in the primary interstitial form, there 
is chiefly atrophy of the cells and a slight degree of fatty change. 

In some cases in which the overgrowth of fibrous tissue is 
very great, we may find fibroid tumors in the pyramids of the 
kidney. 



*3* NOTES ON PATHOLOGY. 

Duration. Chronic interstitial nephritis is a progressive pro- 
cess terminating fatally. 



Frequently certain salts are deposited in the kidney structure. 
Calculi in the kidney itself are rare. 

(a) Uric-acid deposits. These are normal in the newborn and 
are found at the ends of the pyramids. They consist of sodium 
urate and usually disappear in two or three weeks. If persistent, 
they give rise to irritability or uremic symptoms. They are of 
medico-legal importance, as such deposits are only found after 
respiration has been established. Similar deposits, but more 
toward the middle of the pyramids, occur in adults, in cases i 
gout. 

(b) Lime-salt deposits. These are common in advanced life, 
and are seen as grayish lines or as an opacity toward the apices of 
the pyramids. They may lead to calculi in the pelvis or bladder, 
but usually are of no significance. 

Tuberculosis may be embolic, being a part of a general 
miliary tuberculosis, or it may result from extension of the disease 
from the pelvis. The second form may be the only lesion of tuber- 
culosis in the body. Cheesy cavities may be formed, involving the 
pyramids and cortex. 

Syphilis is rare in the kidney. When it occurs, it is usually 
in the form of gummata or scars ; although it is possible that it 
may lead to a diffuse overgrowth of the connective tissue, especially 
in cases of inherited syphilis. 

Tumors. — Benign tumors are rare, although lipomas, 
fibromas, and adenomas are occasionally found. Cancer is rarer 
in the kidney than in other abdominal organs. Primary sarcoma is 
absolutely rare, but as compared with other abdominal viscera, the 
kidney is a relatively frequent seat. The tumor is often congenital, 
and is then usually combined with myxoma or rhabdomyoma. 

TUBE-CASTS. 

These are a part of the inflammatory exudate which has 
moulded itself in the uriniferous tubules. They are composed ot 
an albuminous matrix, the exact nature of which is not known, 
and of elements derived from the renal or the blood cells. There 
are two chief varieties of casts — (a) hyaline, (b) cellular. 



TUBE-CASTS. 2$$ 

(a) Hyaline casts. These consist of an albuminous material of 
obscure composition ; it contains nitrogen and resembles the sub- 
stance formed in various degenerations — amyloid, hyaline, coagu- 
lation necrosis. In some cases the casts are colloid, in others 
mucoid, or amyloid. Waxy casts are a special form of hyaline 
casts — they are opaque, homogeneous, and are composed of a 
material of obscure composition. At times they are amyloid. 

(5) Cellular casts. These are fundamentally also hyaline, but 
have attached to them cells or cellular debris. The following are 
the main varieties : 

(1) Epithelial casts; (2) blood casts; (3) pus casts. Any of 
'these cells, but especially the epithelial cells, may degenerate into 
granular matter, thus giving rise to (4) granular casts. 

Diagnostic value of casts. By themselves casts are insufficient 
to establish a diagnosis of the form of nephritis. The presence of 
cellular casts in large numbers indicates a rapid shedding of the 
epithelium, and hence signifies acute parenchymatous nephritis ; the 
same is true of abundant blood casts. The presence of granular 
casts alone indicates chronic change — if present in abundance, and 
if of large size and fatty, we may infer chronic parenchymatous 
nephritis. When casts are few, and those found are hyaline, the 
case is probably one of chronic interstitial nephritis. 

Cylindroids are long slender casts of a hyaline material, resem- 
bling mucus. They are often bent upon themselves, ribbon-shaped, 
and terminate in a fine whip-like extremity. Their exact meaning 
is not known ; they do not always indicate organic disease, but seem 
usually to be connected with congestion of the kidney. 



*34 NOTES ON PATHOLOGY. 



CHAPTER XIV. 



MICROSCOPIC TECHNIQUE. 

Fixation of Tissues. — This has for its object the preserva- 
tion of the tissues, so that the constituents may retain as nearly as 
possible the characters they possessed during life. It is, therefore, 
obvious that tissues should be fixed immediately upon removal 
from the body. The following agents are employed as fixation 
fluids. 

(a) Alcohol. This has the advantage that it fixes and hardens 
the tissues at the same time, whereas when other fluids are used for 
fixing, the tissues must subsequently be passed through alcohol. 

Small pieces of tissue, not more than 2 or 3 cm. thick, are 
thrown in an excess of 95 per-cent. alcohol, which is changed after 
24 hours. The tissue is then placed for 24 hours in absolute 
alcohol, when it is ready for embedding. 

For delicate work, especially for bacteriologic studies, the 
tissue is best placed at once in absolute alcohol, which is changed 
in 24 hours, the specimen being ready for the embedding process 
at the end of the second day. It is advisable in all cases to place 
a little cotton on the bottom of the bottle, that the lower surface of 
the specimen may not adhere to the glass and be acted upon by 
the alcohoL 

(b) Mutter's fluid. This consists of 

Potassium dichromate , 2.5 grams. 

Sodium sulphate 1.0 gram. 

Water ioo.o c. c. 

The fluid should be greatly in excess of the volume of the 
specimen and should be changed as often as turbid, but during the 
first few days should be changed daily. The specimens may be 
kept in the fluid indefinitely, the minimum time being about three 
weeks, though this limit may be shortened by keeping the bottle in 
the incubator for a time. 

After removal from the Miiller's fluid, the tissue is washed in 
running water for from 4 to 6 hours, and then placed in 70 per-cent. 



MICROSCOPIC TECHNIQUE. 235 

alcohol, and kept in the dark. Every day it is placed in stronger 
alcohol, 80, 90, and 95 per-cent., and finally in absolute alcohol. 
Muller's fluid is cheap and can be used for almost every kind of 
tissue. Nervous tissue should be placed in it and not in alcohol. 

(c) Corrosive sublimate. The solution is prepared by saturat- 
ing a warm 5 per-cent. sodium chlorid solution with corrosive 
sublimate (= 7.5 per-cent). The pieces remain in the fluid from 4 
to 6 hours, are then thoroughly washed for several hours in running 
water to remove the mercurial precipitate, and then are hardened 
by being passed through alcohol of gradually increasing strength 
— 40, 70, 95 per-cent., and absolute, being left 24 hours in each. 

The method is especially useful for tissues removed from the 
living body. 

(d) Formalin. This is a 40 per-cent. solution of formaldehyd. 
Tissues are placed in a 10 per-cent. aqueous solution of formalin, 
and can remain there for an indefinite time. Afterwards they are 
hardened in alcohol, beginning with 50 per-cent. 

(e) Flemming's solution is especially adapted for the study of 
karyokinesis or of fatty changes in the cells. It consists of 

1 per-cent. solution of chromic acid 15 parts. 

2 " " osmic acid 4 " 

Glacial acetic acid . 1 part. 

The specimens, which should be very small, are allowed to 
remain in the fluid for 24 hours, in the dark ; they are then washed 
in water for 24 hours, and subsequently hardened in alcohol ot 
increasing strength. Flemming's solution cannot be kept for any 
length of time. 

(/) Osmic acid, in 1 per-cent solution, is useful when it is 
desired to study fatty changes. The tissues are treated as in the 
case of Flemming's solution. 

(g) ErlickVs fluid consists of 

Potassium dichromate , . 2.5 grams. 

Copper sulphate 0.5 gram. 

Water 100.0 grams. 

This has the advantage over Muller's fluid of fixing in from 8 
to 10 days at room temperature, or in 4 or 5 days in the incubator; 
its disadvantage is that it causes more shrinking and produces a 
precipitate. The specimens are treated as when Muller's fluid is 
used. 



236 NOTES ON PATHOLOGY. 

Embedding. — (a) Celloidin method. This is the method 
most generally employed by pathologists. The celloidin is dis- 
solved in a mixture of equal parts of absolute alcohol and ether. 
It is usually customary to prepare two solutions — a thin one and a 
thick one of about the consistence of syrup. The pieces, after 
thorough dehydration in absolute alcohol, are placed in the first 
solution for 24 hours, and for an equal length of time in the 
second. The specimen is then transferred, with an excess of 
celloidin clinging to it, to a block of dry wood. More celloidin is 
poured about the specimen, and the preparation allowed to become 
firm by evaporation. As soon as an opaque film appears on the 
celloidin, the block is thrown into 80 per-cent. alcohol. 

(b) Paraffin method. After dehydration in absolute alcohol 
(24 hours), the tissue is placed for about 12 hours in chloroform, or 
until the alcohol has been displaced by the chloroform, which is 
indicated by a subsidence of the specimen below the surface. It is 
then placed in a saturated solution of paraffin in chloroform and 
allowed to remain for 12 hours, when it is transferred to pure melted 
paraffin, the melting-point of which is 50 C. It is kept in this for 
about 24 hours, or until the paraffin has completely permeated the 
specimen. Whether this has taken place or not can be determined 
by plunging a heated iron rod into the paraffin near the specimen 
— as long as chloroform is still present, bubbles will be given ofT. 
At the proper time a paper or metallic box is filled with melted 
paraffin, and the specimen transferred into the mould with a warmed 
forceps, care being taken to have the specimen properly placed with 
regard to the plane of cutting. The paraffin is immediately solidi- 
fied by placing the mould in cold water. As soon as the paraffin 
on the surface has congealed into a film, water is allowed to run 
over the mould. 

In hot weather the specimen may be transferred to melted 
paraffin having a higher melting-point before being placed into the 
mould. 

Section Cutting. — (a) For cutting tissues embedded in 
celloidin, the knife is placed obliquely so as to bring the entire 
cutting surface of the blade into use, and is kept moist with 80 
per-cent. alcohol. 

(b) Paraffin specimens are cut dry. When ribbon sections are 
desired, the knife is placed at right angles; otherwise it is set 
obliquely. 



MICROSCOPIC TECHNIQUE. 337 

(c) Frozen specimens. Pieces not more than 3 or 4 mm. thick 
are placed on the metal plate of a freezing microtome and frozen 
by an ether-spray, which is made to play against the under surface 
of the plate. If the tissue has been in alcohol, it should be washed 
free from the latter with water. The tissue should not be frozen 
too hard. Sections are received in 80 per-cent. alcohol or in 0.6 
per-cent. salt solution. 

Tissues fixed in Muller's fluid may be cut on the freezing 
microtome. 

Staining, Clearing, and Mounting. — The methods of 
staining depend upon the special selective affinity which various 
tissue elements show for different stains, and in many respects 
stains are comparable to chemical reagents. By a process known 
as differentiation we are able to produce a staining of certain parts 
of the tissue, while others are deprived of whatever color they have 
taken up from the original stain by the differentiating agent. The 
advantages of differentiation are obvious : First, it brings out more 
clearly the contrast between different elements, usually between 
the nucleus and the cell protoplasm ; secondly, it permits us to 
counterstain the decolorized parts by other stains. 

No fixed limit can be given for the length of time speci- 
mens should be left in the various stains — this must be learned by 
experience. As a general rule the anilin dyes require less time 
than the vegetable stains which, as ordinarily employed, stain in 
from 5 to 10 minutes. It is always necessary to filter the stains 
before using if not clear. 

Clearing. This aims at rendering the tissues transparent, so 
that light can pass through them. The agents used are chiefly the 
essential oils, such as oil of cloves, oil of bergamot, oil of origanum, 
oil of cedar, turpentine, etc., and certain benzine derivatives, such 
as xylol, either alone or combined with carbolic acid. The clearing 
agent most widely used is oil of cloves, which has the advantage 
that it takes up considerable water and completes the dehydration 
of the sections. It possesses, however, the disadvantage of dis- 
solving the celloidin, which renders the handling of delicate sections, 
such as lung tissue, difficult. Oil of bergamot has less dehydrating 
power, but does not dissolve celloidin. 

Xylol, or, more frequently, carbol-xylol, is largely employed 
for sections stained with the anilin dyes, as for such sections the 
essential oils cannot be used since they, -especially oil of cloves, 



238 NOTES ON PATHOLOGY. 

dissolve the dye. Carbol-xylol (xylol 3, carbolic acid 1) and, more 
particularly, xylol, have the disadvantage that they are apt to 
wrinkle the specimens and to render them brittle. 

Sections are left in the clearing agent until they are transparent, 
i. <?., until a dark object can be seen through the specimen. 

The mounting medium most universally employed is Canada 
balsam dissolved in xylol. For mounting specimens of fatty tissue, 
stained with osmic acid, pure balsam should be used. In certain 
special methods sections are at times mounted in glycerin. 

Methods of Staining. I. Staining of Sections.— Sec- 
tions that are embedded in celloidin can be kept in 80 per-cent. 
alcohol until ready for staining. 

A. Hematoxylin. — This is one of the best nuclear stains 
we possess. The solution generally employed is that of Delafield, 
which is prepared as follows : 

(1) Hematoxylin (crystals) 4 grams. 

Absolute alcohol 25 c. c. 

(2) Ammonia alum (crystals) 52 grams. 

Water 400 c. c. 

Mix (1) and (2), and let the solution stand for 4 days exposed 
to light and air, but protected from the dust. The fluid acquires a 
deep-blue color. Filter and add 

(3) Glycerin 100 c. c. 

Methyl alcohol 100 c. c. 

Filter after 5 or 6 hours, and keep in a tightly stoppered bottle 
at least 5 or 6 weeks before using. The solution should be well 
diluted before staining sections. Better results are obtained by long 
immersion in a weak solution, than by brief immersion in a strong 
solution. When sections are overstained, they cannot be satisfac- 
torily decolorized, although it may be done to a certain extent by 
placing the section in a weak solution of hydrochloric acid, and 
subsequently washing in water. 

Water is the differentiating agent in hematoxylin staining. 

Method of staining. 1. Place section in water. 

2. Stain until of a deep-blue color. 

3. Wash in a large quantity of water until excess of stain is 
removed. It is often a good plan to allow section to remain w 
water for 24 hours. 

4. Dehydrate in 95 per-cent. alcohol (2 to 5 minutes) 



MICROSCOPIC TECHNIQUE. 239 

5. Dehydrate in absolute alcohol (1 minute). 

6. Clear in oil. 

7. Mount in Canada balsam. 

B. Lithium Carmin. — The solution consists of 

Carmin 2 grams. 

Saturated aqueous solution lithium carbonate . . . . 100 c. c. 



For differentiation the following solution is employed : 

Hydrochloric acid 1,0 c. c. 

70 per-cent. alcohol 100 c. c. 

Method of staining. 1. Place section in water. 

2. Stain from 3 to 5 minutes. 

3. Place at once into differentiating fluid until section is rose- 
pink. 

4. Wash thoroughly in water to remove the acid. 

5. Dehydrate in 95 per-cent. alcohol. 

6. Dehydrate in absolute alcohol. 

7. Clear in oil. 

8. Mount in Canada balsam. 

C. Borax Carmin. — The solution is made after the follow- 
in? formula : 

Carmin 2.5 grams. 

Borax 4.0 " 

Water 100 c. c. 

75 per-cent. alcohol 100 c. c. 

The carmin and borax are rubbed up in a mortar, and as far 
as possible dissolved in the water, which should be heated. The 
alcohol is then added, the fluid is filtered, and kept in a tightly 
stoppered bottle. The method of using the stain is the same as 
that for lithium carmin. 

D. Bismarck-brown. 

Distilled water 70. 

95 per-cent. alcohol 30. 

Meat to boiling and add 

Bismarck-brown 3. 

Stir and filter. 

The method of staining is as follows : 

1. Transfer section from 70 or 80 per-cent. alcohol into stain. 
Leave in stain 1 or 2 minutes. 



240 NOTES ON PATHOLOGY. 

2. Wash section in 70 or 80 per-cent. alcohol until excess of 
color is removed. 

3. Dehydrate in 95 per-cent. alcohol. 

4. Dehydrate in absolute alcohol. 

5. Clear in oil of bergamot. 

6. Mount in Canada balsam. 

Double Staining, — This consists in the staining of the 
sections with both a nuclear and a protoplasmic stain. 

(a) Hematoxylin and Eosin.— The sections that have 
been stained with hematoxylin and washed in water are dehydrated 
in alcohol to which a few drops of a saturated alcoholic solution 
of eosin have been added. They are left in this until the blue 
color has a slight reddish cast. They are then placed in absolute 
alcohol, cleared in oil, and mounted in balsam. The eosin may be 
added to the absolute alcohol instead to the 95 per-cent. The 
nuclei are blue, the protoplasm and intercellular substance reddish- 
pink. 

(b) Carmin and Picric Acid.— A few drops of a saturated 
alcoholic solution of picric acid are added to the alcohol used 
in dehydrating the sections previously stained with carmin. The 
nuclei are red, while the protoplasm and intercellular substance 
are yellow. 

Special Stains. A. Weigert's Fibrin Stain.— The 

method of using this stain is given on page 34. Before being sub- 
jected to the fibrin stain, the sections may be stained with lithium 
or borax carmin, being subsequently transferred from water or 
alcohol to the gentian-violet solution. The nuclei appear red, the 
fibrin and bacteria blue. 

B. Weigert's Stain for medullated nerve fibers. The 
specimen is kept for several weeks in Muller's fluid, which is 
repeatedly changed. It is then placed, without washing, in 70 
per-cent. alcohol in the dark, and the alcohol changed as long as 
it is made turbid by the potassium dichromate. The specimen is 
further hardened in stronger alcohol, and finally embedded in 
celloidin in the customary manner. The block with the specimen 
attached is then placed for 24 hours in solution No. 1. 

Saturated solution cupric acetate. 
Distilled water, equal parts. 



MICROSCOPIC TECHNIQUE. 241 

The block is transferred to 70 per-cent. alcohol, and cut into 
sections after 24 hours. The sections are stained for 24 hours in 
the following solution (No. 2) : 

Hematoxylin 1.0 gram. 

Absolute alcohol 100 c. c. 

Saturated solution lithium carbonate 1.0 c. c. 

Distilled water 90 c. c. 

They are then washed in a large volume of water and trans- 
ferred for differentiation to solution No. 3 : 

Sodium biborate (borax) 2.0 grams. 

Potassium ferricyanid 2.5 " 

Distilled water 200.0 c. c. 

The sections remain in this for from ^ to 2 or 3 hours, accord- 
ing to the intensity of the stain. They are then washed in water, 
dehydrated in alcohol, cleared in xylol or carbol-xylol, and mounted 
in Canada balsam. Given briefly the method is as follows : 

1. Fix in Miiller's fluid. 

2. Harden in alcohol without previously washing in water. 

3. Embed in celloidin. 

4. Leave block for 24 hours in solution No. 1. 

5. Leave block twenty-four hours in 70 per-cent. alcohol. 

6. Cut. 

7. Stain with solution No. 2, for 24 hours. 

8. Wash in large volume of water. 

9. Differentiate by means of solution No. 3 — from ^ to 2 or 
3 hours. 

10. Wash in water. 

n. Dehydrate in alcohol. 

12. Clear in xylol or carbol-xylol. 

13. Mount in Canada balsam. 

C. Pal's Modification for Weigert's Method for medul- 
lated nerve fibers. This gives very good results and consumes less 
time than the original method. 

1. Fix in Miiller's fluid, harden in alcohol, embed in celloidin. 

2. Place in the copper solution (solution No. 1) for 24 hours. 

3. Place in 70 per-cent. alcohol for 24 hours. 

4. Cut. 

5. Stain sections in Weigert's hematoxylin solution for from 
24 to 48 hours, for the last hour in an incubator. 

16 



242 NOTES ON PATHOLOGY. 

6. Wash in water to which several drops of a saturated solu- 
tion of lithium carbonate have been added, until sections have a 
deep-blue color. 

7. Place for from 20 to 30 seconds in a 0.25 per-cent. solution 
of potassium permanganate. 

8. Place for a few seconds into the following solution : 

Pure oxalic acid 1 .0. 

Potassium sulphid j.o. 

Distilled water 200.0. 

9. Wash thoroughly in water. If the stain is too deep, steps 
7 and 8 may be repeated. 

10. Dehydrate in alchol. 

11. Clear in xylol or carbol-xylol. 

12. Mount in Canada balsam. 

A pretty counterstain is obtained by adding a few crystals of 
magdala-red to the xylol. 

D. Golgi'S Silver Method for nerve cells and their pro- 
cesses. Harden very small pieces in 

-x per-cent. solution potassium dichromate 80 c. c. 

I " " osmic acid 10 c. c. 

Transfer directly to 

Silver nitrate 0.75 grams. 

Distilled water 100.0 c. c. 

The solution is changed in an hour's time. The pieces may 
afterwards remain in the fresh solution as long as desired — 24 hours 
is sufficient. Harden in alcohol, embed in celloidin. Sections are 
cut, dehydrated in alcohol, cleared in turpentine or oil of cloves, 
and mounted in Canada balsam. 

E. Golgi's Corrosive Sublimate Method for nerve cells 
and their processes. Thin pieces of tissue are hardened in M tiller's 
fluid or in 2 per-cent. potassium dichromate solution and then 
placed in 0.25 per-cent. corrosive sublimate solution, which is 
changed as long as it becomes yellow, the strength of the solution 
being gradually increased to 0.5 or 1.0 per-cent. 

Small pieces are stained in from 8 to 10 days; larger ones 
require a longer time. The sections are thoroughly washed, de- 
hydrated in alcohol, cleared in oil, and mounted in Canada balsam. 



MICROSCOPIC TECHNIQUE. 243 

F. Marchi'S Method for nerve fibers : 

1. Very small pieces are placed at once into Miiller's fluid, 
and kept in this for from 1 to 4 weeks. 

2. They are then placed for 6 or 8 days in 

Miiller's fluid 2 parts. 

l per-cent. solution osmic acid 1 part. 

3. Wash thoroughly in water. 

4. Harden in alcohol, embed in celloidin, and cut. 

5. Dehydrate in alcohol, clear in oil, mount in balsam. 

G. Van Giesson's Method. 

1. Harden in Miiller's fluid or in alcohol. 

2. Embed in celloidin, cut sections. 

3. Stain for from 3 to 10 minutes in Delafield's hematoxylin. 

4. Wash thoroughly in water. 

5. Stain for from 3 to 5 minutes in a saturated aqueous solu- 
tion of picric acid, to which a saturated aqueous solution of acid- 
fuchsin is added, until the mixture has a deep-red color. 

6. Wash in water for half a minute. 

7. Dehydrate in alcohol, clear in oil of origanum, mount in 
Canada balsam. 

The sections should be overstained with the hematoxylin, as 
the picric acid decolorizes them to a certain extent. The method 
is employed for staining axis-cylinders, and for colloid, hyaline, and 
mucoid material. 

Method of Staining Sections Embedded in Paraffin. 

— In staining sections embedded in paraffin, it is necessary first to 
remove the paraffin, but as the sections cannot be handled after this 
has been done, they are cemented to the slide before the removal oi 
the paraffin. The methods of staining are the same as for celloidin 
sections. The methods of fixing the section to the slide and dis- 
solving out the paraffin are as follows : 

The slide is painted with a thin layer of a freshly prepared 
mixture of 

Collodion I part. 

Oil of cloves 3 parts. 

The section is placed in position, and the slide gently warmed, 
either over a water-bath or at a considerable height above a naked 
flame, until fumes of oil of cloves appear. In this way the oil is 



244 NOTES ON PATHOLOGY. 

driven off and the section adheres by means of the collodion. The 
paraffin is removed by immersing the slide bearing the section in 
benzol or xylol, and then in turpentine. The turpentine is dis- 
solved out by means of alcohol; the section is then ready for 
staining. 

For very accurate work the following method of fixation is 
employed. The section is floated on the slide with a weak solution 
of gum arabic. The slide is cautiously heated to secure expansion 
of the section, but never to a point at which the paraffin melts. 
The excess of liquid is then drained off, the section finally arranged 
in proper position, and the slide placed in a place where it can dry 
without being exposed to the dust. To insure complete evapora- 
tion of the water, it is advisable to let the slide dry over night. 

Sections thus fixed cannot be treated with watery stains, as 
they are loosened by them. When such stains are to be employed, 
the sections are best cemented on with a weak gelatin solution. 
After the sections have expanded and are properly fastened, the 
slide is soaked in a weak solution of potassium dichromate, which, 
in the presence of light, renders the gelatin insoluble in water. 

II. Staining in Bulk. — This is rarely employed in patho- 
logic studies. 

The piece of tissue, which should not be more than 2 cm. in 
thickness, is placed from 80 per-cent. alcohol into borax carmin. 
The length of time which the piece should remain in the stain varies 
with its size and the density of the tissue — usually 24 hours is 
sufficient. From the carmin the piece of tissue is transferred directly 
to the differentiating solution (see lithium carmin stain), where it 
remains from 24 to 48 hours. When the fluid is no longer colored 
red, it is removed, washed in water, dehydrated in alcohol of in- 
creasing strength, and embedded. 

Staining of Blood Corpuscles on cover-glasses. The 
finger from which the blood is to be taken is washed with soap and 
water, alcohol, and ether, and with a needle or a small spear-pointed 
knife a bold puncture is made in the pulp of the finger. The top 
of the exuding drop is touched with a perfectly clean cover-glass 
held in the bite of a forceps. This cover-glass is at once super- 
imposed upon another cover-glass, also held in a pair of forceps ; 
the two cover-glasses are then slid apart and allowed to dry in 
the air. 



MICROSCOPIC TECHNIQUE. 245 

There are two methods of fixing the blood to the cover-glass. 

{a) EhrlicWs method. The cover-glass is heated on a bar ot 
copper to 120° or 130 C. 

(b) Nikiforoff's method. The cover-glasses, dried in air, are 
placed for from yd to 24 hours in a mixture of equal parts of abso- 
lute alcohol and ether. This is a very good and simple method. 

For ordinary purposes the specimens are stained for one 
minute in 

Eosin 0.5 grams. 

70 per-cent. alcohol 100.0 c. c. 

They are then washed in water, and stained for one minute in a 
saturated aqueous solution of methyl-blue, or for a longer period in 
Delafield's hematoxylin, well diluted with water. 

The eosin stains the red corpuscles and the eosinophile granules 
in the leukocytes ; the methyl-blue or hematoxylin stains the nuclei 
of the white corpuscles. 

The neutrophile and eosinophile granules of the leukocytes may 
be stained simultaneously by means of Ehrlich's triple stain : 

Sat. aqueous solution orange G , 125 c. c. 

Sat. solution (in 20 per-cent. alcohol) acid-fuchsin ... 125 c. c. 
Add gradually, stirring constantly, 

Sat. aqueous solution methyl-green 125 c. c. 

Then add 

Absolute alcohol 75 c. c. 

The solution is allowed to stand for several weeks, and is not 
filtered. In using the solution the quantity needed should be 
removed with a pipette from near the middle of the bottle. 

The specimen is stained from 2 to 5 minutes with the solution, 
washed in water, dried in air, and mounted in balsam. The red 
corpuscles are colored orange, the nuclei of the leukocytes and of 
nucleated red corpuscles green, the neutrophile granules violet, and 
the eosinophile granules red. 

Biondi's mixture is practically the same. The solution con- 
sists of 

A filtered sat. aqueous solution aurantia ...... 100 c. c. 

A sat. solution acid-fuchsin 20 c. c. 

Sat. solution methyl-green 50 c. c. 

For staining this solution must be diluted with 100 parts of 
water, and enough acetic acid added to give it a deep-red color. 



246 NOTES ON PATHOLOGY. 

Biondi's stain may be obtained in solid form, and need only be 
dissolved prior to using. 

Basophile granules may be stained with the following solution : 

Sat. aqueous solution methyl-blue 40.0 

0.5 per-cent. solution eosin in 70 per-cent. alcohol . . . 20.0 
Distilled water . 40.0 

The cover-glasses are stained in this solution in the incubator 
at 37 C, for from 3 to 6 hours. The eosinophile granules appear 
red, the basophile granules blue.* 



* The most reliable stains are those prepared by Dr. Griibler, of Leipzig. They can be obtained 
from several firms in this country. 



BACTERIOLOGY. 



INTRODUCTION. 



Although bacteriology is one of the youngest of sciences, we 
nevertheless find dim suggestions of it in the writings of classical 
antiquity. It is with the theories of spontaneous generation, fer- 
mentation, and putrefaction that its origin seems to be most inti- 
mately connected. In regard to the first it was the prevailing belief 
until a comparatively recent date that life could, under certain 
favorable conditions, develop spontaneously. Among the early 
Greek philosophers we find a number (Anaximander, Empedocles, 
Aristotle, and others) advocating this theory. From their time, 
down through the middle ages, no one seems to have questioned 
the possibility of the origin of life de novo. 

Francesco Redi, who, in 1668, demonstrated that maggots did 
not develop spontaneously, but were the larvae of flies, was one of 
the first to throw doubt on the truth of the theory. The dis- 
covery of bacteria by Leeuwenhoek, in 1675, revealed a class of 
organism the minuteness of which suggested not only a close rela- 
tionship to the ultimate molecules of matter, but also an easy transi- 
tion from them, and thus strengthened the belief in spontaneous 
generation. 

Spallanzani, in 1777, found that when organic infusions con- 
tained in hermetically sealed flasks were boiled, they did not there- 
after become putrid. This was at first explained by ascribing it to 
the exclusion of oxygen, but Schulze, in 1836, showed that if 
such flasks were supplied with air that had been passed through 
sulphuric acid, no life developed, in spite of the admission of oxygen. 

In 1837, Cagniard de Latourand Schwann, independently, dis- 
covered that the yeast-cell was the cause of alcoholic fermentation. 
Pasteur, finally, in 1862, brought incontrovertible proof of the fact 
that the development of life in organic infusions exposed to the air 
was due to the organized particles floating in the atmosphere and 



2 NOTES ON BACTERIOLOGY. 

falling into the fluids. And he also showed that these bodies were 
capable of causing putrefaction as well as fermentation. 

In regard to certain diseases, it was suggested by Henle, in 
1840, that they had a living cause, a " contagium vivum" probably 
of a vegetable nature. 

Pollender, in 1849, and Davaine, in 1850, observed the anthrax 
bacilli in the blood of animals suffering from splenic fever, and in 
1863, Davaine claimed to have demonstrated by inoculation the 
causal relationship between the bacillus and the disease. His con- 
clusions were rejected at the time because he had used the blood of 
the diseased animal, which, it was urged, might have contained some 
other entity, the bacilli being present accidentally only. 

Klebs, in his work on " Septicemia and Pyemia," published in 
1872, expressed himself convinced that the causes of these diseases 
must come from without. In 1873 Obermeyer discovered the 
spirillum of relapsing fever. The introduction of the anilin dyes, 
by Weigert, in 1877, made a much more thorough investigation of 
bacteria possible, and discoveries soon became so numerous and 
convincing that it was impossible to doubt that micro-organisms were 
the causes of many diseases. In 1878 Koch published his important 
treatise on "The Traumatic Infectious Diseases." In 1879 Hansen 
discovered the bacillus of leprosy, and Neisser the gonococcus. In 
1880 Pasteur published his memoir on chicken- cholera, and in the 
same year Sternberg discovered the micrococcus Pasteuri, now 
known as the peumococcus. 

The typhoid fever bacillus was in this year discovered by 
Eberth and, independently, by Koch. The year 1880 is also mem- 
orable on account of the discovery of the plasmodium malarias, the 
cause of malarial fever, by Laveran. In 1882 Koch announced 
his great discovery of the tubercle bacillus. In the same year 
Pasteur published his researches on " Rouget du pore," and Loffler 
and Schiitz the discovery of the bacillus of glanders. In 1884 
Koch described the comma bacillus or spirillum of cholera ; Loffler 
the diphtheria bacillus, and Nicolaier the bacillus of tetanus. Be- 
tween the years 1884 and 1892 few important discoveries were made, 
most of the work done consisting in the perfection of the methods 
of investigation. In 1892 Cannon and PfeifTer, independently, dis- 
covered the bacillus of influenza. In 1894 Kitasato discovered a 
bacillus in the lesions of plague. 



CHAPTER 



BACTERIA. 

A bacterium is a minute organism consisting of a single cell, 
principally composed of an albuminous substance called myco- 
protein. In ioo parts of dried bacteria there are found : 

Myco-protein 84.20 parts. 

Fat 6.04 " 

Ash 4.72 " 

Undetermined 5.04 '* 

The myco-protein is generally homogeneous, but may be 
granular, as in bacillus megatherium ; sometimes it contains granules 
of chlorophyl, sulphur, fat, or pigment. Each cell is surrounded 
by a cell-wall which in some species gives the cellulose reaction 
with iodin. With the ordinary nuclear stains it is possible to dis- 
tinguish between the nucleus and the cell- wall ; but when stained 
with the anilin-dyes, which have a much greater penetrating power, 
the bacteria appear as solidly colored spheres, spirals, or rods, as 
the case may be. 

Some bacteria are surrounded by a capsule, the formation of 
which probably depends upon peculiar changes in the cell-wall. 

BIOLOGY. 

Organisms which take into their bodies particles of food, digest 
that which is useful, and extrude the remainder, are animals, while 
those that imbibe nutrient fluids only by osmosis through a cell- 
wall, are vegetables. 

Bacteria, since they live by osmosis and exosmosis, belong to 
the vegetable kingdom. Their extremely simple organization places 
them in the lowest class of the cryptogamia, or flowerless plants, 
that known as Thallophytes. These are divided into three groups : 

(a) Alga. These are chiefly water-plants containing chloro- 
phyl, and obtaining their nourishment from inorganic substances. 

3 



4 NOTES ON BACTERIOLOGY. 

(6) Lichens. These live upon inorganic matter, generally 
absorbed from the air; some contain chlorophyl, others do not. 
By many it is now held that lichens are fungi growing parasitically 
upon algae. 

(c) Fungi. These, the lowest group, live upon organic matter, 
either as saprophytes y upon decomposing organic matter, or as para- 
sites, upon living animals and plants. They are as a rule devoid of 
chlorophyl. 

The fungi are divided into 

1. Hyphomycetes, mucorini, or moulds. 

2. Saccharomycetes, or yeasts. 

3. Schizomycetes, or bacteria. 

Bacteria have been classified in a multitude of ways ; the best 
classification is probably that based on the general shape of the 
individual. 

(1) Cocci. — Spherical bacteria. 

(2) Bacilli. — Rod-shaped bacteria. 

All those having one diameter greater than the other should 
be classed among the bacilli. 

(3) Spirilla. — Spiral-forms, twisted like corkscrews. 
The cocci are subdivided into 

(a) Micrococci. Perfect spheres, except during fission, when 
they are oval. 

(/3) Diplococci. Cocci occurring in pairs. The contiguous sur- 
faces may be flattened or, as in the gonococcus, slightly concave. 

(7) Tetragonococci. Cocci dividing in two directions, on the 
•same plane, forming tetrads. Merismopedia is the name given to 
the entire class of cocci dividing, on the same plane, so as to pro- 
duce fours, eights, twelves, etc., 

(<f) Sarcince. Cocci dividing in three directions, so as to pro- 
duce cubical masses or packages, which resemble miniature bales of 
cotton. 

(3) Streptococci. Cocci dividing only in one direction, the 
individuals remaining attached to each other, so as to form chains. 
When diplococci divide in this manner, strepto-diplococci are pro- 
duced. 



BIOLOGY. 5 

(C) Staphylococci. Cocci occurring in irregular groups, re- 
sembling bunches of grapes. 

(77) Ascococci. Cocci arranged in globular or lobulated clusters, 
encased in a firm, gelatinous substance. 

(#) Leukonostoc. Cocci occurring in chains or as solitary indi- 
viduals, surrounded by a gelatinous envelop of almost cartilaginous 
consistence. 

The bacilli vary greatly in size ; some occur always singly, 
others form chains ; some have rounded, others square ends. 

The following names are employed in describing bacilli : 

(a) Leptothrix. Long chains of bacilli without distinct sep- 
aration. 

(f) Myconostoc. Long threads surrounded by a jelly-like 
material. 

(y) Drum-stick. A bacillus with a bulbous end, due to the 
presence of a spore. 

( 6 ) Clostridium. A bacillus distended at its center by a large 
spore. 

Besides these there are a few bacillus-like forms that are not 
easily classified. These are : 

Streptothrix and Cladothrix. Bacilli in single or bundled 
threads, grouped so as to give the appearance of false branching. 

Beggiatoa. A form consisting of indistinctly separated threads 
which are thicker than those of leptothrix. 

Vibrio, a term now rarely used, was formerly applied to flexible 
bacilli possessing an undulating motion. 

The spirilla are twisted like corkscrews. The name spirillum 
is reserved by some for the inflexible spiral forms, while the spiral, 
undulating form is termed spirocheta. 

Other varieties are : 

Spiromonas. A ribbon-shaped spiral organism. 

Spirulina. A spindle-shaped spiral form. 

Ophidiomonas. A variety of spiral forms containing sulphur- 
granules. 

Bacteria vary greatly in size, and on account of their minute- 
ness a special unit of measurement, the micro-millimeter, or micron 
(abbreviated /<), has been adopted. It is 10 1 00 millimeter or 2g ^ 0Q 
inch. 



6 NOTES ON BACTERIOLOGY. 

As a rule the cocci are the smallest, the spirals the longest. 
Cocci vary from 0.15 p to 2.8 p\ bacilli from 1 n to 5 p, in length, 
and from 0.2 //to 1.5 p in width. Some of the spirilla are very long 
e. g., that of relapsing fever measures at times 40 p. 

Bacteria are changed in appearance by different methods of 
preparation. The presence of spores gives rise to an alteration of 
form ; while young bacilli are shorter than older ones. The char- 
acter of the nutrient medium also affects the shape ; in old cultures 
we frequently find distorted shapes, the so-called involution forms. 
Temperature, air, and light likewise exert an influence upon the de- 
velopment of bacteria. But the effect produced by all these agencies 
is slight in the case of cocci, bacilli, and spirilli, these groups being 
subject to the law of co?tstancy of form. This law is generally stated 
as follows : " Although a micro-organism may modify its form and 
habit of life to accommodate itself to its environment, it is within 
certain limits only that this change is possible, and under all circum- 
stances one well-defined form exists, which expresses the type of the 
species." 

On account of their constancy of form cocci, bacilli, and spirilla 
are termed moiiomorphic. 

Cladothrix, beggiatoa, and others, which do not present the 
same form at all times, are called pleomorphic. 

Reproduction. — Bacteria multiply in two ways : 

1. By direct division. When the conditions of nutrition are 
good and growth is active, bacteria multiply by direct division or 
fission. 

2. By sporulation — the formation of spores or seeds. When 
the conditions of growth cease to be favorable, a minute, oval, 
highly refracting body appears in the protoplasm of the bacterium. 
This is the spore. It is peculiarly resistant to the action of heat, 
light, and chemical agents, and to drying, and when transported to a 
suitable culture-medium, looses its wall and rapidly develops into a 
bacterium. 

There are two kinds of spores : 

(a) Endospores — those formed within the protoplasm of the 
bacterium. This form of sporulation occurs in bacilli and spirilla, 
each organism giving rise to a single spore. 

(b) Arthrospores. These are produced by the conversion of 
the entire organism into a spore, a process most common in cocci. 



BIOLOGY. 7 

The general character of spores indicates that they are a pro- 
tective form which the bacteria assume when the conditions of 
growth cease to be favorable. 

Motion. — Many bacteria possess the power of locomotion. 
This, as a rule, depends upon the presence of flagella or cilia, which 
may project from the sides, from one, or from both ends of the 
bacterium. Motility is an attribute of bacilli and spirilli chiefly ; only 
one or two cocci are known to move by means of flagella. But the 
presence of cilia does not necessarily imply motion ; thus, the bacillus 
coli has many flagella, yet it does not move. It has been suggested 
that, besides serving to transport the organisms from place to place, 
flagella may stimulate the passage of currents of nutrient material 
past the bacteria so as to increase the food supply. 

Flagellate bacteria are more common in water, and in fermenting 
and decaying matter than in the bodies of animals. 

There is one organism, the bacillus megatherium, which pos- 
sesses a limited ameboid movement. 

The cocci and small bacilli sometimes present an oscillating or 
dancing movement. This is the so-called Brownian movement ; it 
is a physical phenomenon, and is not accompanied by any change 
in the relative position of the bacteria. 

Distribution. — Bacteria are very widely distributed, but are 
not ubiquitous. They live in the air, in water, in our food, on the 
skin, and in the parts of the body communicating with the exterior. 
But it has been fully established that the blood, lymph, and tissues 
of the healthy animal body are free from bacteria of all kinds. At 
high Alpine altitudes no bacteria are found. The upper layers of 
the soil contain micro-organisms in abundance, but below the depth 
of one meter their number is very small. The presence of bacteria 
in the air is generally dependent upon their previous existence in 
the soil, its pulverization and distribution by currents of the atmos- 
phere. The majority of atmospheric bacteria are saprophytic, but 
owing to the carelessness and neglect of the public, many pathogenic 
organisms also infest the air. As long as tuberculous patients ex- 
pectorate upon the streets and sidewalks, the atmosphere will eontain 
tubercle bacilli, which are set free from the dried sputum and wafted 
through the air. The lack of proper disinfection leads also to the 
perpetuation of such diseases as diphtheria and typhoid fever. 



8 NOTES ON BACTERIOLOGY. 

CONDITIONS INFLUENCING THE GROWTH OF 
BACTERIA. 

The growth of bacteria is profoundly influenced by environ- 
ment. 

1. Oxygen. Bacteria are divided into two great groups, accord- 
ing to the influence of oxygen upon their growth, (a) aerobic 
bacteria — those requiring oxygen for their growth, (b) anaerobic 
bacteria — those not growing when oxygen is present, as the bacillus 
of tetanus and the bacillus of malignant edema. Aerobic forms that 
grow as well without as^wjthjoxygen are termed optional ox facultative 
anaerobic. 

2. Nutriment Bacteria grow best where diffusible albumins 
are present, but the amount of nutrient material needed varies 
greatly in different varieties. Sometimes a species with a peculiar 
affinity for a certain culture-medium can gradually be accustomed . 
to another. Sometimes the addition of glucose or glycerin has a 
favorable influence in this respect. Thus the tubercle bacillus can 
be made to grow upon agar-agar to which glycerin has been added, 
although it does not develop upon ordinary agar-agar. 

3. Water. A certain amount of water is always necessary, the 
best growth occurring when the proportion of moisture is about 80 
per-cent. 

4. Reaction. With few exceptions, bacteria grow best in a 
neutral or faintly alkaline medium. Acid media are good for the 
cultivation of moulds. 

5. Light. The direct rays of the sun and, to a less degree, the 
electric arc -light, retard the growth of and frequently kill bacteria. 
Certain colors, as blue, for instance, are distinctly inhibitory to their 
growth. Some chromogenic bacteria produce their pigment only 
when exposed to the ordinary, diffuse light of the room. 

6. Electricity. Very little is known about this, but powerful 
currents are said to check the development of bacteria. 

7. Movement. Perfect rest is most favorable to the growth of 
bacteria. A slow flowing movement of the medium has no inhibitory 
action, but violent shaking disturbs their growth. For this reason, 
a swiftly-flowing stream, the current of which is broken by falls and 
rapids, will, other things being equal, furnish purer drinking water 
than a deep, still-flowing river. 



CONDITIONS INFLUENCING THE GROWTH OF BACTERIA. 9 

8. Temperature. The majority of micro-organisms grow best at 
the temperature of a comfortably-heated room. Many, however, 
only thrive at the temperature of the body, 37 C. Below io° and 
above 40 very few bacteria can grow. A ternperature of 6o° kills 
most bacteria ; boiling for fifteen minutes is fatal to bacteria, but not 
to spores. In order to destroy spores, an exposure to a dry heat of 
150 C. for one hour, or to a heat of 175 ° C. for five to ten minutes, 
is required. Freezing kills most bacteria, but not all ; upon spores 
it has no influence. 

Bacteria are divided into (a) parasitic forms, those the natural 
habitat of which is the animal body, and (b) saprophytic forms, those 
living on decaying animal and vegetable matter. 

The first group is again divisible into the purely parasitic , which 
are never found outside of the tissues or secretions of the animal 
body, and the occasionally parasitic, which live both in the animal 
organism, where they may produce disease, and outside of it, in 
water or air. Of the former, the tubercle bacillus, of the latter, the 
spirillum of cholera, is an example. 

Results of the Vital Activity of Micro-organisms. — 1. Fer- 
mentation. Alcoholic fermentation is produced by the yeast-plant, 
saccharomyces cerevisiae. Acetic acid, lactic acid and butyric acid 
fermentation are brought about by bacilli. 

It is very probable that several species of bacteria are capable 
of setting up each of these latter forms of fermentation, although 
the bacillus aceticus or mycoderma aceti the bacillus acidi lactici, 
and the bacillus butyricus are most active in the production of their 
respective acidsrC 

2. Putrefaction. This is the decomposition of nitrogenous 
substances under the influence of bacteria. The process gives rise, 
during its intermediate stages, to peptone-like substances, to 
aromatic compounds, and to certain alkaloidal bodies, known as 
ptomains. Many of the peptone-like bodies and of the ptomains 
are poisonous. A ptomain is a chemical compound, basic in 
character, formed by the action of bacteria on organic matter 
( Vaughan and Novy). The most important ptomains are methyl- 
amin, trimethylamin, propylamin, putrescin, cadaverin, neuridin, 
saprin, tyroxicon, etc. 

3. Chrornogenesis , or pigment-production. Bacteria that produce 
pigment are termed chromogenic ; those that do not, non-chromogenic. 
The majority of chromogenic bacteria are saprophytic ; a few are 



io NOTES ON BACTERIOLOGY. 

parasitic. All colors of the spectrum are met with. The pigments 
have been separated into two classes, a soluble pigment, which pene- 
trates the culture medium, and an insoluble one, which does not 
tinge the culture medium, but is only found in the bacterial growth. 
The majority of the pigments are only produced in the presence 
of oxygen and light. 

4. Liquefaction of gelatin. This is due to the action of a 
peptonizing ferment produced by the bacteria. The power oi 
liquefying gelatin is possessed only by certain species. 

5 . Production of acids. Several bacteria give , rise to the 
formation of acids in the culture media, the quantity increasing 
until the acidity is so intense as to stop the growth of the organisms. 
The development of acids is detected by adding litmus to the 
culture medium. Rosalie acid may also be used. 

6. Production of gases. C0 2 , H 2 S, NH 3 , are the more common 
varieties of gases produced. 

7. Production of odors. Some bacteria produce characteristic 
odors, independent of the gases mentioned above. 

8. Production of phosphorescence. Several varieties of bacteria 
produce phosphorescence, as the bacillus phosphorescens of sea- 
water. 

9. Production of aromatic compounds. Indol is the most 
important, and is produced by the cholera spirillum and other 
micro-organisms. 

10. Reduction of nitrites. Several bacteria are capable of 
reducing the nitrites in the soil or in specially prepared culture media 
into ammonia and nitrogen. 

1 1 . Production of disease. Bacteria are divided into pathogenic, 
or disease-producing bacteria, and non-pathogenic ', or those which 
do not produce disease. The pathogenic bacteria may be parasitic 
or saprophytic. There is no sharp line of separation between patho- 
genic and non-pathogenic bacteria, for certain of the former may be 
deprived of their disease-producing power, and some of the latter 
may be rendered pathogenic by special manipulations or by com- 
bining them with other bacteria. The exact mode in which bacteria 
cause disease varies. Some multiply so rapidly as to block the 
blood- and lymph-channels ; others merely act as foreign bodies 
which the tissues attempt to eliminate. More important than either ot 
these effects, however, is the production of poisons — toxim or ptomains 
— by the bacteria. These toxic products may cause a widespread 



CONDITIONS INFLUENCING THE GROWTH OF BACTERIA. n 

destruction of the tissues immediately acted upon, or, circulating 
with the blood, produce fever and peculiar nervous phenomena. 
The pyogenic bacteria induce suppuration by generating a chemo- 
tactic substance or by killing tissue-cells, which subsequently unfold 
chemotactic properties. Bacteria may, therefore, produce disease : 

(a) By obstructing the lymph- and blood-channels. 

(b) By acting as foreign bodies. 

(c) By generating poisons. 

(d) By inherent chemotactic properties, or by destroying cells 
which become chemotactic. 

Channels of Infection. — Bacteria gain entrance into the body 
through the following channels : 

1. The digestive tract. The micro-organisms of many diseases 
enter the digestive tract with the food and drink. The majority do 
not pass beyond the stomach, as they are killed by the acid gastric 
juice. When the latter is deficient or the bacteria are peculiarly 
virulent, they may reach the intestines and develop in the alkaline 
juices. 

2. The respiratory tract. This is the common channel of intro- 
duction of the tubercle bacillus, the pneumococcus, and the influenza 
bacillus. 

3. The skin and superficial mucous membranes. Few bacteria 
can penetrate the healthy, unbroken skin or mucous membrane. 
It is probable that in those experiments in which infection was 
caused by rubbing bacteria or their spores upon the skin, minute 
lesions were produced, through which the germs entered. 

4. Distinct wounds. The entrance of bacteria through wounds 
is a frequent occurrence ; yet the majority of infectious diseases 
and nearly all the distinctly contagious diseases, arise without the 
existence of any visible wound. 

5. Heredity. There is no doubt at the present time that the in- 
fectious agent of a number of diseases can be transmitted to the 
fetus in utero. The infection may occur at the time of conception, 
and be derived from either parent, or post conceptionem, from the 
mother. This congenital infection has been observed in small- 
pox, measles, syphilis, typhoid fever, pneumonia, malaria, tubercu- 
losis, and other diseases. 



NOTES ON BACTERIOLOGY. 



CHAPTER II, 



SUSCEPTIBILITY AND IMMUNITY. 

Susceptibility is that condition of the animal organism in which 
it is a fit soil for the growth of pathogenic bacteria or for the action 
of bacterial poisons. 

Immunity is the opposite — it is a condition in which the animal 
body resists the development of micro-organisms or the action of 
their poisons. 

Immunity is either natural or acquired. 

i. Natural immunity. This is the constant resistance which 
certain animals (and human beings) exhibit toward certain diseases. 
The lower animals are immune to typhoid fever and to cholera. 
Most birds and reptiles resist anthrax, while man, sheep, cows, 
rabbits, and white mice are susceptible to it. Morphologic differences 
may explain variations in immunity among animals of dissimilar 
families ; but as we find marked variations in the species of the 
same family, other factors must also be present. We find, for 
instance, that Europeans and Americans are susceptible to the poison 
of scarlet fever, while the Japanese are generally immune to it. 
Among the lower animals, the house-mouse, field-mouse, and white 
mouse, although resembling each other in all respects except 
color, differ very much in their susceptibility to disease. 

2. Acquired immunity. This may be naturally or artificially ac- 
quired. Naturally acquired immunity is that which remains after 
recovery from certain infectious diseases. Thus one attack of yellow 
fever or of typhoid fever protects, as a rule, against a second attack 
of the same disease. Immunity may be artificially produced in the 
following ways : 

(i) By operations upon the animal: 

(a) By vaccination, as in the case of small-pox. 

(b) By injecting blood-serum from an immune animal or from 
one convalescent from a certain disease, as tetanus, into a suscepti- 
ble animal. 

(2) By manipulation of the specific organism. The pathogenic 
power of bacteria may be weakened in various ways. The condition 



SUSCEPTIBILITY AND IMMUNITY. 13 

of lessened virulence is called attenuation, and may be produced by- 
cultivating the bacteria under unfavorable conditions. 

Immunity, it should be remembered, is only relative, and an 
animal that is immune to a quantity of germs sufficient to kill 
another animal of similar size, will probably succumb to a quantity 
sufficient to kill a very large animal. 

Susceptibility varies greatly. Young animals are generally 
more susceptible than older ones. Lowered states of nutrition and 
exhaustion increase the susceptibility. A susceptible state may be 
produced in animals ordinarily immune, (1) by altering the body- 
chemistry, either by a change in diet or by the introduction into 
the body of certain substances ; (2) by changing the environment, 
principally as regards temperature ; (3) by diminishing the strength 
of the animal ; (4) by the removal of certain organs, as the spleen ; 
(5) by injecting combinations of different species of bacteria, each 
alone of which might be harmless ; (6) by intensifying the virulence 
of bacteria by previous inoculation into very susceptible animals, or 
by growing them upon special culture media ; (7) by introducing 
large doses of bacteria. 

The following theories have been advanced in explanation of 
the phenomena of immunity : 

1. The exhaustion theory. In 1880, Pasteur advanced the 
theory that, by its growth in the body, the micro-organism uses up 
some substance essential to its life, and that when this substance is 
exhausted, the body is no longer a fit soil for the micro-organism. 

2. The retention theory. It was suggested by Chauveau, also 
in 1880, that the growth of the bacteria in the body might generate 
some substance prejudicial to their farther and future development. 

3. The theory of phagocytosis. In 1881, Carl Roser drew 
attention to the possible relation between immunity and phagocyto- 
sis. Sternberg and Koch also observed the phenomena of 
phagocytosis, but little attention was paid to the subject until 
Metchnikoff, in 1884, ascribed the production of immunity to these 
phenomena. 

Phagocytosis is the englobing of foreign particles by certain 
cells called phagocytes. These are divided into fixed phagocytes 
(endothelial cells, connective tissue cells, etc.), and free phagocytes 
(principally leukocytes). Not all leukocytes are phagocytes — 
lymphocytes, or cells with a large nucleus and a small amount of 
protoplasm, are not phagocytic, while the large uninuclear and 



14 NOTES ON BACTERIOLOGY. 

multinuclear forms are. The large uninuclear leukocytes are known 
as macrophages, the small multinuclear forms and those possessing 
a single nucleus in the process of breaking up, as microphages. 
Phagocytosis is intimately associated with the phenomena of chem- 
otaxis. Chemotaxis is the relation or force existing between ameboid 
cells and food particles. If the cells are attracted to the food 
particles we speak of positive chemotaxis ; if they are repelled or 
not attracted, of negative chemotaxis. 

Phagocytosis is not a rare phenomenon. In relapsing fever, in 
erysipelas, and in other infectious diseases, the bacteria can be found 
within leukocytes at the time of subsidence of the active processes. 
But the opponents of the phagocytic theory insist on the probability of 
the bacteria having been dead &ef ore they were swallowed by the cells. 
Metchinkoff answered this objection by showing that leukocytes en- 
globed spores, and that when they were conveyed to a proper culture 
medium, the spores were set free and developed into bacilli. 

The micro-organisms which are seized by the leukocytes are 
carried to the spleen and the lymphatic glands. 

4. The humoral theory. It was frequently observed that when 
bacteria were introduced into drawn blood a large number of 
them were speedily killed. From this fact, and others of a similar 
nature, such as the death of bacteria placed in blood serum, in 
aqueous humor, and in other body fluids, Buchner and others con- 
cluded that the destruction of micro-organisms in the body was 
brought about by the bactericidal action of the blood-plasma. 

5. The theory of defensive proteids. This is a modification of 
the humoral theory, and predicates the existence in the body of 
immune animals of proteids possessing the power of destroying the 
bacteria or of neutralizing the poisons generated by them. Buchner 
termed these protective proteids alexins, while Hankin classified 
them into two groups, designating those that occur in naturally 
immune animals, sozins y and those found in animals with acquired 
immunity, phylaxins. A sozin capable of destroying bacteria he 
called myco-sozin, and the corresponding phylaxin, myco-phylaxin. 
Toxo-sozin and toxo-phylaxin counteract the bacterial poisons. 
The defensive proteids are now generally termed antitoxins. Their 
existence has been established in tetanus, diphtheria, pneumonia, 
and other diseases. 

None of the theories cited above is entirely satisfactory, and 
much remains to be done before the subject of immunity is clear. 



METHODS OF OBSERVATION. 15 



CHAPTER III. 



METHODS OF OBSERVATION. 

One of the first essentials for the study of bacteria is a good 
microscope, the features of which are a set of good lenses, in- 
cluding an immersion-lens with a clear magnifying power as high 
as 1000 diameters, and a good light condenser. 

Rules for using the microscope with the oil immersion-lens : 

1. Employ good glass-slides and thin cover-glasses (No. 1). 

2. Place a drop of cedar-oil on the cover-glass, rack the body 
of the instrument down until the oil immersion-lens meets the oil 
and almost touches the glass-cover, and then find the object by 
slowly racking |up. As soon as the object comes into view, focus 
with the fine adjustment. 

3. Select the light from a white cloud if possible ; avoid the 
direct sunlight. 

4. In using the high powers the condenser must be brought 
near to the object and the diaphragm opened so as to admit a large 
amount of light. The contrary is to be observed when low power 
lenses are employed. When the bacteria are unstained the amount 
of light admitted should be less than when they are stained. 

Examination of Unstained Bacteria. — The simplest method 
is the examination in the hanging drop, for which a slide having a con- 
cavity in the center is used. With a camel's hair brush a ring of 
vaselin is smeared around the concavity. A drop of the material 
to be examined is placed in the center of a perfectly clean cover- 
glass. If the material is solid, a drop of distilled water is first 
placed on the cover-glass, and the material then mixed with it. The 
cover-glass is now placed upon the slide so that the drop hangs into 
the concavity without touching. The cover-glass is held by the 
vaselin, and as the latter prevents evaporation, the preparation will 
keep for days. 

The hanging drop should always be studied at its edge y as the 
center is too thick. 



1 6 NOTES ON BACTERIOLOGY. 

The following points are to be observed : 

1. Shape and size of the organisms. 

2. Motility. 

3. Grouping (chains, threads, etc.). 

4. Sporulation. 

Examination of Bacteria in the Stained Condition. — For 
the staining of bacteria we now employ, thanks to the great dis- 
covery of Weigert, the anilin dyes. These are coal-tar products, 
and represent almost every conceivable shade of color. The 
majority are derived from anilin-oil, a few from the naphthalin 
group. A good practical division is that into basic and acid dyes. 

Basic dyes are fuchsin, gentian-violet, methyl-violet, methyl- 
blue, bismarck-brown, etc. 

Acid dyes are eosin and acid-fuchsin. 1 

The anilin dyes are always employed in solutions. For the 
general staining of cover-glass preparations, we first prepare a stock 
solution of the dye. These are saturated alcoholic solutions and 
are made by adding one part of the dye to four of alcohol. The 
stock solutions do not stain bacteria, but are the standards from 
which the working stains are made in the following simple way : 
A small bottle with a pipette stopper is nearly rilled with distilled 
water, and enough of the stock solution added until the transpa- 
rency disappears. Such a watery solution penetrates the proto- 
plasm of the bacteria, while the alcoholic solution does not. 

Method of Making a Cover- Glass Preparation. — A little of 
the substance to be examined is spread upon a clean cover-glass 2 in the 
thinnest layer possible, and allowed to dry in the air. The material 
is then fixed to the glass — i. e., the albumin in the bacteria is coagu- 
lated, so that it adheres to the glass, and will not be removed when 
the latter is washed. This is accomplished by placing the dried 
cover-glass for twenty-four hours in a mixture of equal parts of 
absolute alcohol and ether or, as is simpler and more rapid, by 
passing the cover-glass, smeared side up, three times through the 
flame of a Bunsen burner or an alcohol lamp. The preparation is 
now ready for the stain. The cover-glass being held in a special 
kind of forceps, enough of the stain is dropped on from a pipette to 
cover it. The stain is allowed to remain on two to three minutes, 



1 The best anilin dyes are those sold by Dr. Griibler, of Leipzig. 

2 Cover-glasses may be cleaned by placing them for a time in H 2 S04, then washing them in water 
and in alcohol. They are kept in ether. 



METHODS OF OBSERVATION. 17 

after which the cover-glass is thoroughly washed in water. It is 
now mounted in water and examined. If found good, it may be 
removed from the slide, dried, and permanently mounted in Canada 
balsam. 

Synopsis of the method : 

1. Spread material on cover-glass. 

2. Dry in air. 

3. Fix by passing thrice through flame. 

4. Stain two or three minutes. 

5. Wash in water. 

6. Dry. 

7. Mount in Canada balsam. 

For some micro-organisms special stains, possessing greater 
penetrating power than the simple watery solutions, are required. 

The important ones are the following : 

Ehrlich's Solution. — This is a solution of any basic anilin 
dye in anilin oil and water. It is made as follows : 

Anilin oil 4 parts 

Distilled water 100 " 

Shake well ; filter, and add 

Saturated alcoholic sol. of dye 1 1 " 

Filter. 

This is used principally for staining the tubercle bacillus and 
in staining by Gram's method ( Vide infra). 

As Ehrlich's solution does not keep longer than six to eight 
weeks, it may be prepared in small quantity by pouring about one 
cubic centimeter of anilin oil into a test-tube, filling the tube about 
one-half with distilled water, shaking the mixture well, then filtering 
into a small dish. To this the saturated alcoholic solution of the 
basic dye is added until the surface becomes distinctly metallic in 
appearance. 

Lbffler's Solution ; 

Saturated alcoholic sol. of methyl-blue 30 

Watery solution caustic potash ( 1 ton 0,000) 100 

This is especially useful in staining the typhoid bacillus. 
Ziehl's Solution : 

Fuchsin 1 

Alcohol 10 

5 per- cent watery solution carbolic acid crystals .... 90 

2 



18 NOTES ON BACTERIOLOGY. 

This is chiefly employed in staining the tubercle bacillus. 

Staining of Bacteria in Tissues. — Unless the specimen of 
tissue is properly preserved the bacteria rapidly degenerate and 
lose their power of absorbing the stain. It is best to cut very small 
pieces and fix them immediately in absolute alcohol or in bichlorid 
of mercury solution. 

Before staining it is advisable to remove the celloidin ; if paraffin 
has been used as the embedding material, it must be dissolved out. 
The method of staining is briefly as follows : 

1. Float the section out in water. 

2. Into watery solution of the stain, 5 to 8 minutes. 

3. Wash in water, 3 to 5 minutes. 

4. Decolorize the tissue in 0.1-0.5 per-cent solution of acetic 
acid for 30 seconds. 

5. Dehydrate in alcohol. 

6. Place in absolute alcohol for a short time. 

7. Clear in xylol (not in oil of cloves). 

8. Mount in Canada balsam. 

The tissue may be counterstained after differentiating with 
acetic acid. If the original dye used was blue, Bismarck-brown or 
alum carmin are adapted for this purpose. 

Instead of the simple watery solution of the stain, Loffler's alka- 
line methyl-blue solution may be used with advantage. 

Gram's Method. — This depends upon the principle that when 
bacteria that have been stained in Ehrlich's solution, are placed 
in a solution of iodin and potassium iodid, a new compound is 
formed in their protoplasm which is insoluble in alcohol. 

This insoluble compound (of mycoprotein, basic dye in anilin 
oil, and iodid) is formed by many but not by all bacteria ; there are a 
number of important species which do not form it, and, hence, are 
jiot stained by Gram's method. They are the micro-organisms 
of Asiatic cholera, chicken cholera, malignant edema, glanders, 
gonorrhea, relapsing fever, typho[d_J^ver, rabbit septicemia, and 
the bacillus pneumoniae of Friedlander. 

Gram's method for cover-glass preparations. 
Spread material upon cover-glass, dry, and fix. Stain for 2 to 5 
minutes with Ehrlich's solution, keeping the stain warm by holding 



METHODS OF OBSERVATION. 19 

the cover-glass over a flame. Pour off the stain, and place the 
cover-glass for y 2 to 2 minutes in the following solution : 

Iodin I 

Potassium iodid 2 

Water 300 

Next wash the cover-class in 95 per-cent alcohol until almost 
no color remains ; then counterstain with eosin or Bismarck-brown. 
Dry, and mount in Canada balsam. Given briefly the method is as 
follows : 

1. Ehrlich's solution, 2-5 minutes. 

2. Gram's solution, ^-2 minutes. 

3. Wash in 95 per-cent alcohol until decolorized. 

4. Dry. 

5. Mount in Canada balsam. 

Gram's method for sections. 
Given briefly, this is as follows : 

1. From alcohol or water into Ehrlich's solution made with 

gentian-violet, 1-5 minutes. 

2. Wash in water. 

3. Into iodin solution, 2 minutes. 

4. Wash in 95 per-cent alcohol until almost decolorized. 

5. Dehydrate in absolute alcohol. 

6. Clear in xylol. 

7. Mount in Canada balsam. 

The sections may be counterstained after decolorization, with 
eosin or Bismarck-brown. Or they may be stained in advance with 
lithium-carmin or picro-carmin. 

Method of Staining Spores. — Spores are not easily stained. 
The best methods seem to be the following: (a) Spread the 
cover-glass in the thinnest layer possible; dry and fix. Then 
float on a watch- glassful of Ehrlich's solution, made with fuchsin, 
and heat until steam arises, allowing the cover-glass to remain in 
the hot solution 5 to 15 minutes. Transfer it to a 3 per-cent solu- 
tion of HC1 in water, for 1 minute ; then wash in water, and coun- 
terstain with an aqueous solution of methyl-blue. The spores 
appear red, the bacilli blue. 

(b) For the spores of many species the following method 
seems to give good results: Boil the prepared cover-glass for 15 
minutes in a test-tube half full of carbol-fuchsin solution (Ziehl's 
solution q. v.). Decolorize in a 3 per-cent HC1 or 2-5 per-cent 
acetic acid solution ; wash in water, and counterstain with methyl-blue. 



20 NOTES ON BACTERIOLOGY. 

Method of Staining Flagella. — This is even more difficult 
than the staining of spores. The best method is that devised by 
Loffler, for which three solutions are required. 

A. 20 per-cent solution of tannic acid 10 

Cold saturated aq. solution of ferrous sulphate ... 5 
Alcoholic solution of fuchsin or methyl-violet .... I 

B. 1 per-cent solution of caustic soda. 

C. An aqueous solution of H 2 S0 4 of such strength that 

one cubic centimeter will exactly neutralize an equal 
quantity of solution B. 

Two cover-glasses are prepared with a drop of distilled water 
on each. Some of the bacteria to be stained are mixed with the 
drop of water on the one cover-glass, and from this a small portion 
is mixed with the second, this being the only one used, as the first 
contains too many bacteria. After drying, the cover-glass is passed 
three times through the flame, being held in the fingers instead of in 
the forceps. Solution A is now poured on and warmed until steam 
arises ; but it must not be boiled. The solution is allowed to act 
for y 2 to 1 minute. The cover-glass is then washed in water, then 
in absolute alcohol until all traces of the solution have been re- 
moved. The real stain — Ehrlich's solution, made with fuchsin — is 
now poured on, and heated for a minute ; it is then washed off, and 
the cover-glass dried and mounted in Canada balsam. The Ehrlich's 
solution should have a perfectly neutral reaction. This may be 
attained by adding sufficient of solution B to change the transparent 
solution to an opaque one. If the procedure has not succeeded, it 
is necessary to study the products elaborated by the micro-organ- 
ism ; if they are alkaline, solution B in the proportion of from 1 
drop to 1 c. c. is added to 16 c. c. of the mordant A, and the stain- 
ing repeated again and again until the proper amount is obtained. If 
the bacterium produces acids, solution C must be added to the 
mordant in a similar manner. 

The staining of flagella is extremely difficult ; each bacterium 
seems to react differently to the stains. Loffler has determined for 
some of the bacteria the amounts of solutions B and C that must 
be added to 16 c. c. of solution A to attain the desired result. 

Cholera spirillum, ^ to I drop of solution C. 

Typhoid fever bacillus, I c. c. of solution B. 

Bacillus subtilis, 28 to 30 drops of solution B. 

Bacillus of malignant edema, 36 to 37 drops of solution B. 



STERILIZATION AND DISINFECTION. 21 

Bunge's Method of Staining Flagella. 
Bunge recommends the following mordant : 

Concentrated aqueous sol. of tannin 3 parts. 

Sol. of liq. ferri chloridi (1 to 20) I " 

To 10 c. c. of this solution 1 c. c. of a concentrated watery 
solution of fuchsin is added. The bacteria are stained with this for 
5 minutes, the solution being warmed towards the end. The cover- 
glass is washed, dried, and finally stained with a warm carbol-fuchsin 
solution. 

STERILIZATION AND DISINFECTION. 

The destruction of bacteria by means of heat is termed steriliza- 
tion ; their destruction by the action of chemical agents, disinfection. 
The chemical agent which kills the bacteria is called a germicide. An 
object which is entirely free from bacteria and their spores is sterile. 
Substances that prevent the growth of bacteria without necessarily 
killing them are known as antiseptics. 

The study of sterilization, disinfection, and antisepsis falls under 
the following heads : 

I. Sterilization of instruments and apparatus used in experi- 
mentation. 

II. Sterilization of culture media. 

III. Disinfection of instruments, ligatures, hands, etc., of the 
surgeon, and the use of antiseptics. 

IV. Disinfection of sick chambers and their contents, as well 
as the dejecta of patients suffering from infectious diseases. 

I. The sterilization of instruments and apparatus used in experi- 
mentation. This is accomplished either by moist or dry heat. 
Glassware is sterilized by dry heat, in the hot-air oven, at a tempera- 
ture of 150 C, maintained for one hour. The platinum zvire and 
a few other instruments are exposed to the naked flame. Knives, 
scissors, etc., may be heated in the flame, but as a too long expos- 
ure destroys their temper, they are best sterilized in the steam appar- 
atus. It is obvious that unless properly protected sterilized objects 
soon become again contaminated with bacteria. Flasks and test- 
tubes, before being sterilized are plugged with cotton ; this prevents 
the entrance of germs into the sterilized flasks. Instruments may 
be sterilized wrapped in cotton, or may after sterilization be wrapped 
in sterile cotton until required for use. 



22 NOTES ON BACTERIOLOGY. 

IT. Sterilization of culture media. For this purpose the inter- 
mitteiit, or fractional method of sterilization is employed. It consists in 
the exposure of the culture media in flasks or tubes to the action of 
streaming steam for 1 5 to 30 minutes, for three successive days. The 
rationale of this method is that streaming steam kills all bacteria, but 
not the spores. The latter develop in the interval between the first 
and second sterilization ; the newly-formed bacteria are killed by a 
second sterilization at the end of 24 hours. Lest a few spores remain 
and develop, the media are sterilized after 24 hours for the third time. 

III. TJw disinfection of instruments, ligatures, the hands, etc. 
Various chemical substances have been used as disinfectants for those 
objects and parts which cannot be exposed to the naked flame, to 
dry or to steam heat. Among the compounds employed are mercuric 
chlorid, hydrogen dioxid, creolin, thymol, potassium permanganate, 
boric acid, carbolic acid, creasote, alcohol, formalin. The value of 
disinfectants and antiseptics is relative and varies with the micro- 
organism upon which they act. The action of disinfectants is a 
chemical one, the destruction of the bacteria being due to the com- 
bination of the germicide with the mycoprotein. Some of the dis- 
infectants and antiseptics, such as mercuric chlorid and silver nitrate, 
are precipitated by albumins, which fact limits the scope of their 
usefulness. Carbolic acid seems to be the most reliable of all germi- 
cides and antiseptics. 

Disinfection of the hands is carried out as follows : The nails 
should be short and clean. The hands are washed thoroughly for 
10 minutes with brush, soap, and water. The excess of soap is 
washed off in warm water. The hands are then immersed ]/ 2 min- 
ute in a warm saturated solution of potassium permanganate and 
then placed into a warm saturated solution of oxalic acid until com- 
plete decolorization of the permanganate has occurred, after which 
they are washed in sterile water or salt solution. They are finally 
soaked for 2 minutes in a 1 to 500 solution of bichlorid of mercury. 

Surgical dressings are sterilized by superheated steam ; liga- 
tures and sutures, after having been boiled, are kept either in alcohol 
or in an alcoholic solution of bichlorid of mercury ; or, if this 
renders them brittle, in a watery solution of the bichlorid. Instru- 
ments are boiled in water and subsequently kept during the operation 
in a 5 per- cent warm carbolic acid solution. The practice of pour- 
ing boiling water over the instruments just before the operation 
does not sterilize them efficiently. 



STERILIZATION AND DISINFECTION. 2$ 

Instruments, the temper of which is not destroyed by a great 
heat, may be dipped in alcohol and the latter ignited. 

During the operation the wound is frequently washed with 
carbolic acid solution or bichlorid of mercury, I to 2000, applied 
with sterile sponges or pieces of absorbent cotton. 

IV. The disinfection of sick chambers, dejecta, etc. 

(a) The air of the sick-room. It is impossible to sterilize the 
air of the sick-room — free ventilation is the best method of purify- 
ing it while the patient is in the room, afterward sulphur fumes 
may be used ; but more reliance is to be placed upon disinfection 
of the walls and floor and wooden parts of the furniture, combined 
with fresh air and sunlight, than upon fumigation. 

(b) The dejecta, sputum, etc. The vomit, expectoration, etc., in 
diphtheria, should be received in old cloths, which are immediately 
burnt. Tuberculous sputum is expectorated into glazed earthen 
vessels that can be subjected to boiling or disinfection, or into rice 
paper napkins, which are promptly burnt. The excreta of typhoid 
fever and cholera patients are received in glazed earthen vessels 
and intimately mixed with a 5 per-cent solution of chlorid of lime, 
if semi-solid, or with the powder, if liquid, and allowed to stand for 
an hour. 

(c) The clothing, etc. All clothing that has been in contact 
with the patient, should be disinfected by means of steam ; when 
this is not possible, prolonged boiling is the best substitute. When 
applicable, the clothing should be soaked in 1 to 2000 bichlorid 
solution before or after boiling. 

(d) The walls and floor of the room. The walls and ceiling 
should be rubbed with fresh bread, which collects the bacteria, and, 
if possible, should also be whitewashed. The floors should be 
scoured with a 5 per-cent solution of carbolic acid, or 1 to 1000 of 
bichlorid of mercury. 

(e) The patient after convalescence should be bathed daily with 
a weak bichlorid of mercury solution, or with a 2 per-cent carbolic 
acid solution, or with 25 to 50 per-cent alcohol. In desquamative 
diseases, the distribution of epidermic scales may be prevented by 
anointing the body with a simple unguent. 

The dead that have perished of infectious diseases, should be 
washed in strong disinfectant solutions and speedily buried with 
great privacy, or, preferably, cremated. 



NOTES ON BACTERIOLOGY. 



CHAPTER IV. 



CULTIVATION OF BACTERIA— CULTURE MEDIA. 

For the study of bacteria as well as for the determination of 
their relation to disease-processes, to fermentation, to putrefaction, 
etc., it is necessary to isolate the different species from each other, 
and to observe them in pure culture. Very little organic matter is 
necessary for the growth of bacteria, but considerable moisture — 
about 80 per-cent of water — is needed. In cultivating the patho- 
genic forms of micro-organisms, a medium approximating the 
composition of the juices of the body is most serviceable. 

The following are some of the more important culture media : 

Bouillon or Meat Infusion. — To 500 grams of finely- 
chopped lean beef 1000 c. c. of water are added. This is allowed to 
stand for twelve hours on ice. At the end of that time the liquor 
is decanted, that remaining in the meat is expressed through a 
cloth, and enough water added to bring the total amount again to 
IOOO c. c. To this 10 grams of Whitte's peptone and 5 grams of 
salt are added, and the whole boiled until the albumins are coagu- 
lated. The solution, made acid by the sarcoiactic acid of the meat, 
is now neutralized, or rendered faintly alkaline, by means of a satu- 
rated watery solution of sodium carbonate. It is allowed to cool 
and then filtered. It may be kept in flasks, or be dispensed in 
sterile test-tubes — about 10 c. c. in each tube — and is finally steril- 
ized by the intermittent method of sterilization previously described. 
Instead of the 500 grams of meat, bouillon may be prepared with 
extract of beef (Liebig's) in the following way : To 1000 c. c. of 
water add 10 grams of Whitte's peptone, 5 grams of sodium 
chlorid, and about 2 grams of beef extract. Boil the solution, neu- 
tralize, and filter when cold. 

Bouillon is the basis of culture media ; from it gelatin and agar- 
agar can be readily prepared. 

Gelatin. — This is prepared as follows : To 1000 c. c. of meat 
infusion, or to 1000 c. c. of water containing 2 grams of beef ex- 
tract, 10 grams of peptone, 5 grams of salt, and 100 grams of 
gelatin (" Gold-label "), are added, and the whole boiled in a kettle 



CULTIVATION OF BACTERIA— CULTURE MEDIA. 25 

for an hour over a moderately hot flame. The mixture should be 
stirred occasionally. It is allowed to cool to 6o° C, and then neutral- 
ized with a saturated solution of sodium carbonate. The white of an 
egg beaten up in water is next added, and the mixture boiled for 
half an hour longer. It is then, while still warm, filtered through a 
pharmaceutical filter. Finally, it is distributed into sterilized tubes, 
and sterilized by the fractional method. 

The advantages of gelatin consist in that it is an excellent nu- 
trient medium for bacteria, and that it is a transparent solid, which 
can be made liquid and subsequently re-solidified. 

Agar-agar. — This is a peculiar Japanese sea-weed which 
dissolves in boiling water and forms a thick jelly when cold. It 
remains solid at temperatures at which gelatin melts, and can be 
kept in the incubator without becoming liquid. 

To 1000 c. c. of bouillon, made as above described (preferably 
with meat instead of beef-extract), 10 grams of agar-agar are 
added, and the mixture boiled for an hour, the water lost by evapo- 
rization being always replaced. Then it is cooled to 6o° C, and 
after neutralization, an egg beaten up in water is added, and the so- 
lution boiled again. It is then filtered through a folded filter. 
Filtration is somewhat tedious, and the filter-paper has to be 
renewed. It is best to pour on about half of the solution and add 
the hot remainder when necessary. 

If made from beef-extract the agar-agar nearly always precipi- 
tates a considerable amount of urates as it cools. 

The agar-agar is dispensed in tubes, and sterilized by the inter- 
mittent method. After the last sterilization the tubes, before 
cooling, are laid on an inclined plane so as to offer an extensive 
flat surface for the culture. 

Glycerin-agar is made by adding about 5 per-cent of glycerin 
to the melted agar-agar prepared as detailed above. It constitutes 
an excellent culture medium for the tubercle bacillus. 

Blood-serum. — This is obtained from a slaughter-house. The 
blood is received in a glass jar sterilized by heat or by washing 
with alcohol and ether. 

It is advisable to avoid the first blood which comes in 
contact with the hair. The clot is separated from the sides of the 
vessel by means of a sterilized glass rod and the jar placed in an 
ice chest for from 12-24 hours. The clear serum is then trans- 
ferred into test-tubes (about 8 c.c. to a tube) by means of a sterilized 



26 NOTES ON BACTERIOLOGY. 

pipette. If it is desired to use the serum in a liquid form, it is 
sterilized by exposing it for an hour on five consecutive days to a 
temperature of from 6o° to 65 ° C. If a solid medium is wanted 
the tubes are exposed twice, or three times if contamination is 
feared, to a temperature just short of the boiling point, for one and 
one-half hours each time. The tubes should always be inclined 
before the serum is coagulated. There are a few bacteria that 
liquefy blood-serum. 

Loffler's Blood-serum Mixture. — This consists of 

Blood-serum 3 parts. 

Meat infusion bouillon containing 1 per-cent of glucose . . . 1 part. 

It is placed into tubes and sterilized exactly like blood-serum. 

Potatoes. — The most satisfactory method of preparing potatoes 
for culture media is that devised by Bolton and Globig. 

With a cork borer a number of cylinders are cut from large 
potatoes. They are cut transversely so that several, each about one 
and one-half inches in length, can be made from a single potato. 
The skin is removed from the ends and each cylinder cut in two by 
an oblique incision. The half-cylinders are placed into sterilized 
test-tubes with their oblique surface up, and the tubes subsequently 
sterilized by steam for 20 minutes on three consecutive days. 
The disadvantage of the potato as a culture medium is that it soon 
becomes dark and dry. Drying may be prevented by placing a few 
drops of water in each tube before sterilizing. 

Milk. — This is a good culture medium but must before using 
be deprived of its cream. It is best to secure fresh dairy milk from 
which the cream has been removed by a centrifugal machine. After 
distribution into tubes it is sterilized by steam. 

Litmus Milk. — This is milk to which enough of a watery solu- 
tion of litmus has been added to give it a faint blue color. Should 
the milk be acid, it is necessary to add a few drops of a sodium 
carbonate solution. Litmus milk is used to determine whether 
bacteria by their growth produce acids. 

Peptone or Dunham's Solution. — The composition of this is 
as follows : 

Sodium chlorid 0.5 

Dried peptone 1. 

Water 100. 



CULTURES AND THEIR STUDY. 27 

After boiling until the ingredients have dissolved, the solution 
is filtered. It is an excellent medium for the detection of indol. 
The addition of rosalic acid makes of it a good medium for the 
determination of acids in cultures. A solution of rosalic acid is 
made by dissolving rosalic acid 0.5 in water 100; of this 4 c. c. are 
added to 100 c. c. of Dunham's solution. The pale rose color of 
the mixture fades under the action of acids, and is intensified 
under that of alkalies. 

CULTURES AND THEIR STUDY. 

A growth of micro-organisms in which immense numbers are 
massed together is called culture. If such a growth contains but 
one kind of organism it is known as a pure culture. There are 
three principal methods for preparing pure cultures, those by means 
of Koch's plates, of Petri's dishes, and of Esmarch's tubes. 

1. Plate cultures. Half a dozen glass plates are cleansed and 
then sterilized in a hot-air oven. A moist chamber, or double dish, 
is disinfected with 1 to 1000 bichlorid of mercury solution and a 
sheet of bibulous paper placed on the bottom, and moistened with 
the disinfecting solution. The plates are then leveled by means of 
a special leveling apparatus, over a vessel of ice-water. Several 
tubes, usually three, of melted gelatin at the temperature of about 
37 C, are now inoculated with the material containing the bacteria 
in such a manner as to make what are known as dilutions. To do 
this one of the tubes is inoculated with a sterile platinum loop or 
Oese from the material to be studied ; from this tube the second one 
is inoculated, and from the second the third tube. The last tube 
contains such a small number of bacteria that the individual 
colonies, subsequently developed, will not coalesce and can be 
observed with ease. After the tubes have been thus prepared the 
stoppers are removed and the ends of the tubes held for a moment 
in the flame ; the contents are then poured out upon the cold glass 
plates, and after the gelatin is solidified, the latter are placed in the 
moist chamber. Where each organism falls, a colony soon develops, 
from which tubes can be inoculated and pure cultures obtained. 

2. Petri dishes. These are small double dishes that are so 
convenient that they have almost entirely displaced the glass plates. 
The dishes are sterilized, the test tubes prepared as described, and 
the contents poured into the dishes, which are properly marked and 
set aside for the colonies to develop. 



28 NOTES ON BACTERIOLOGY. 

3. Esmarch Tubes. The tubes are prepared in the usual way, 
but should contain a smaller quantity of the culture medium. 
Several are inoculated and then twisted about in ice-water so as to 
spread the contents on the sides of the tubes. 

Gelatin, agar-agar, and glycerin-agar can be used for plating ; 
blood-serum cannot. 

The offspring of each bacterium forms a mass which is termed 
a colony. The colonies should be studied with the naked eye and 
with a low power of the microscope ; drawings of them should be 
made at intervals. 

A pure culture, when it is to be obtained from colonies growing 
upon a plate, must always be made from a single colony, the colony 
being touched with the platinum-wire under the microscope and then 
transplanted into a culture tube. 

Puncture cultures are made by puncturing the gelatin with the 
platinum-wire carrying the bacteria all the way down to the bottom 
of the tubes. 

Stroke cultures are made upon agar-agar or blood-serum by 
drawing the wire over the inclined surface of the medium from the 
bottom to the top. 

The development of bacteria in liquid culture media is of less 
interest than that upon solid media. The growth generally mani- 
fests itself by a diffuse turbidity. Some forms grow most rapidly 
at the surface of the liquid and produce a distinct membranous 
pellicle, called a mycoderma. Others produce a growth chiefly 
below the surface and form gelatinous masses which are known as 
zooglea. 

Much attention has recently been bestowed upon the prepara- 
tion of sections of the gelatin growth in puncture culture. One 
method consists in fixing the gelatin in Muiler's fluid. To do this 
the tube is warmed sufficiently to allow the gelatin to be removed 
to the fluid ; after fixation, the gelatin is passed through alcohols 
of increasing strength, imbedded in celloidin, cut, and stained just 
as tissue sections are. 

Another convenient method is to bore a hole in a block of 
paraffin, soak the block for an hour in bichlorid of mercury solu- 
tion, then to pour the liquid gelatin into the cavity, allowing it to 
congeal, and afterwards inoculating it. After the growth has 
developed sufficiently, sections are cut under alcohol and stained 
with very dilute carbol-fuchsin. 



EXPERIMENTATION UPON ANIMALS. 29 

Permanent specimens of plate and puncture cultures in gelatin 
can be made by treating, simultaneously, the gelatin and the micro- 
organisms with for matin, in spray or in dilute solution. 

THE CULTIVATION OF ANAEROBIC BACTERIA. 

This is always attended with difficulty, and none of the 
numerous methods proposed is entirely satisfactory. 

The method now generally employed is as follows : The inocu- 
lations are deeply made in culture media as free from air as possible, 
e. g., into freshly steamed agar-agar. The tubes are loosely plugged 
and placed in an air-tight chamber, the bottom of which contains 
pyrogallic acid — pyrogallic acid 1 , solution of caustic potash 1 , water 
10. The apparatus is connected on one side with an exhaust pump, 
on the other with a hydrogen apparatus by which means the 
atmosphere is removed and replaced by hydrogen. The chamber 
is then permanently sealed and the germs allowed to grow. What- 
ever oxygen may have escaped the exhaustion is at once absorbed 
by the pyrogallic acid. 

The recognition of bacteria is difficult, and it is often necessary 
to apply all the methods of bacteriologic technique in order to 
differentiate one species from another. Only a few possess such 
marked peculiarities of growth, color, or staining as to be readily 
distinguished from all others. A series of tables has been com- 
piled by Eisenberg which is a valuable guide in determining the 
name of a species. 



CHAPTER V. 



EXPERIMENTATION UPON ANIMALS. 

Experimentation upon animals is indispensable for the study 
of the causes of infectious diseases and for the preparation of cura- 
tive agents against them. Wanton cruelty to the animal should be, 
and is, avoided by the conscientious experimenter. 

Two principal methods of introducing bacteria are employed, 
the subcutaneous and the intravenous injection. Subcutaneous 



3Q NOTES ON BACTERIOLOGY. 

injections are made exactly as hypodermatic injections are given in 
man. In the intravenous method the needle of the syringe is intro- 
duced into a superficial vein ; in the rabbit, for instance, into the 
vein on the dorsal surface of the ear. 

Sometimes intra-abdominal and intra- pleural injections are 
made, and occasionally pieces of fresh tissue, such as particles of 
tuberculous glands, are introduced under the skin or into the ab- 
dominal cavity. 

The inoculation can at times be made with the platinum-wire 
through a small opening in the skin. 

In making autopsies on infected animals it is necessary to use 
antiseptic precautions to exclude foreign germs. The animal should 
be washed with a disinfecting solution and all instruments carefully 
sterilized. 



CHAPTER VI. 



TUBERCULOSIS. 

Tuberculosis is one of the most common diseases of mankind^ 
and is responsible for an immense number of deaths annually. Its 
ravages are, however, not confined to man, but extend to most of 
the domesticated mammalia and also to birds. 

Its cause, though long suspected to be a parasite, especially by 
Klebs, Villemin, and Cohnheim, was not discovered until 1882, 
when Koch succeeded in demonstrating and isolating the specific 
bacillus. 

The tubercle bacillus is a rod-shaped organism with rounded 
ends and a slight curve, measuring from 1.5 to 3.5 n* in length, and 
.2 to .5 /* in breadth, and occurring in pairs or chains, often present- 
ing a beaded appearance. The beading was at one time considered 
to be due to the presence of spores, but is now generally ascribed 
to contraction of the fragmented protoplasm within the resisting 
capsule. The organism is not motile and does not possess flagella. 
The bacillus is peculiar in its reaction to anilin dyes ; it is difficult to 
stain, but also holds the color tenaciously when stained, resisting 
the decolorizing power of strong mineral acids. 



TUBERCULOSIS. 31 

Methods of Staining. — If the material to be examined is 
sputum, it is advisable to select one of the small caseous granules 
usually present in the expectoration of tuberculous patients. This is 
spread on a clean cover-glass ; the latter is dried in the air and passed 
three times through the flame for purposes of fixation. There are 
two principal methods of staining, the Koch-Ehrlich, which is the 
best, and Gabbett's, which is the most convenient. 

(a) Koch-Ehrlich Method. The prepared cover-glasses are placed 
on, or sections are placed in, Ehrliclis solution made with gentian- 
violet, and kept in an incubator for 24 hours. On removing the 
specimens they are momentarily washed in water, and then placed 
for about 30 seconds in jj per-cent nitric acid, then immediately 
into water. They are now washed with 60 per-cent alcohol until 
the blue color is almost entirely lost. If desired, they may be 
counterstained with eosin or Bismarck-brown. The excess of stain 
is washed off in water, the cover-glass is dried and mounted in bal- 
sam, the section is dehydrated, cleared in xylol, and mounted in 
Canada balsam. The bacilli appear blue, everything else pink 
(eosin) or brown (Bismarck-brown). 

A valuable method for sections is that of Unna. The sections 
are placed in a dish of Ehrlich's solution 24 hours old, and allowed 
to remain 12-24 hours at the room temperature or 1-2 hours in the 
incubator. They are then placed in water for 10 minutes, and after- 
wards for 2 minutes in 20 per-cent nitric acid, where they become 
greenish-black. From the acid they are transferred to absolute 
alcohol, and are gently moved to and fro until the pale blue color 
returns. They are then washed in three or four changes of water 
until they become almost colorless. From the water they are re- 
moved to a slide with a section lifter. The water is absorbed with 
bibulous paper, and then the slide heated over a flame until the 
section becomes shining, when it receives a drop of xylol balsam 
and a cover-glass. Sections stained in this manner are said not to 
fade as quickly as those stained by the Koch-Ehrlich method. 

(b) Gabbett's Method. This is more rapid and more convenient. 
The prepared cover-glass is stained with Ziehl's carbol-fuchsin 
solution, 3-5 minutes, the stain being heated over the flame until 
white vapors arise; the cover-glass is then withdrawn from the 
flame for a little while, and then reheated. Care should be taken 
to replace the stain lost by vaporization. After the staining is com- 
pleted, the cover-glass is washed in water and then treated for jo 



32 NOTES ON BACTERIOLOGY. 

seconds, for purposes of differentiation and counterstaining, with 
Gabbett's solution. This consists of 

Methyl-blue 2 

Sulphuric acid 25 

Water 75 

The cover-glass is now thoroughly washed in water, dried and 
mounted in Canada balsam. 

The method may be applied to sections in the following man- 
ner : The imbedding material having been removed, especially if it 
be paraffin, the section is floated out in water, a clean slide placed 
beneath it, and the section lifted on the slide. It is then thoroughly 
dried with bibulous paper, by vigorous rubbing, and stained with 
carbol-fuchsin for from 10-20 minutes, the stain being kept hot 
over a flame. The stain should be replaced as quickly as it evapo- 
rates. The section is washed in water, and then decolorized and 
counterstained with Gabbett's solution, this being permitted to act 
for from 45-60 seco?ids. It is now washed by dropping on alcohol 
from a pipette until a faint blue tinge remains. It is then dried 
with bibulous paper and mounted in Canada balsam. The method 
may be epitomized as follows : 

For Cover Glasses. For Sections. 

1. Spread, dry, and fix. 1. Spread on slide and dry. 

2. Stain with carbol-fuchsin, 3-5 min- 2. Stain with carbol-fuchsin, 10-20 

utes, heating stain. minutes, heating stain. 

3. Wash in water. 3. Wash in water. 

4. Differentiate and counterstain with 4. Differentiate and' counterstain with 

Gabbett's solution, 30 seconds. Gabbett's solution, 45-60 seconds. 

5. Wash in water. 5. Wash in water. 

6. Dry. 6. Wash with alcohol. 

7. Mount in Canada balsam. 7. Dry. 

8. Mount in Canada balsam. 

The bacilli are stained red, everything else is blue. 

The tubercle bacillus also stains well by Gram's method, but 
as this stains other bacteria, it is not adapted for purposes of 
differentiation. 

So far as is known the tubercle bacillus is a purely parasitic 
micro-organism. It is found only in the bodies of animals affected 
with tuberculosis and in their excretions and discharges and in the 
dust that has been contaminated with the latter. 

A pure culture is generally obtained as follows : A guinea-pig 
is inoculated with tuberculous material, allowed to live a month or 



TUBERCULOSIS. 33 

six weeks, and is then killed. Under antiseptic precautions a 
lymphatic gland or splenic nodule is removed, incised, and some of 
the material transferred with a platinum-wire to a blood serum or 
glycerin agar tube. The tubes are then closed with a rubber cap 
placed over the cotton stopper or by a rubber cork above the cotton 
which is cut off and pushed in. The tubes are then kept at a tem- 
perature of 37°-38° C, in the dark. The first growth will be 
apparent in about two weeks in the form of small, dry, whitish flakes. 
If now transplanted to another tube, a more active growth is obtained. 
The tubercle bacillus maybe grown upon glycerin gelatin and upon 
potato, and after it has been grown for many generations on appro- 
priate media, also on agar-agar. But little use is made, however, of 
any culture media save glycerin agar and blood serum. 

The bacillus requires considerable oxygen ; it does not grow 
at a temperature lower than 29 C. or higher than 42 C. Tem- 
peratures above 75 ° C. speedily kill it. Sunlight is also detrimental 
to its growth. 

It was at one time believed that the tubercle bacilli were 
ubiquitous in our atmosphere and that all persons were constantly 
inhaling them in large numbers. Cornet has shown that tubercle 
bacilli exist only in^the atmosphere of places frequented or occupied 
by consumptives. He collected the dust from different localities — 
streets, houses, hospital wards, etc. — and injected it into guinea- 
pigs. He found that the dust contaminated with sputum produced 
tuberculosis in the inoculated animals. 

In order to limit the spread of the disease certain hygienic 
measures are necessary. All tuberculous cases should be registered 
for the purpose of collecting accurate data ; domiciliary disinfection 
should be practiced, and special hospitals erected, particularly for 
the poorer classes among which sanitary measures cannot be well 
carried out. The physician should instruct his patients and their 
friends concerning the danger of infection and the means of 
avoiding it. The patient should have his own eating and drinking 
utensils, his own towels and handkerchiefs; the sputum should be 
properly disinfected. 

Channels of Infection. — (a) The respiratory tract is the most 
common channel. The bacilli may for a time remain dormant in the 
bronchial lymphatic glands. 

(b) The gastro-intestinal tract. The infection is introduced 
with the food, principally with milk from tuberculous cows, and less 



34 NOTES ON BACTERIOLOGY. 

frequently with meat from tuberculous animals. The mesenteric 
glands are generally involved, with or without the co-existence of 
intestinal ulcers. At times the thoracic duct becomes affected; 
general miliary tuberculosis is then readily produced. 

(c) The sexual apparatus. In tuberculosis of the testicle the 
bacilli may be carried with the semen into the sexual organs of the 
female and set up tuberculous lesions in them. 

(d) Inoculation through wounds. Infection through this chan- 
nel is rare. It is seen in the anatomic wart which frequently is 
tuberculous. 

(e) Through the placenta — Heredity. A few instances of trans- 
mission of the bacilli from the mother to fetus through the placenta 
are on record. The bacilli may remain latent in the fetus and cause 
the development of the disease after birth. 

Dead tubercle bacilli are chemotactic, and cause abscesses 
when injected subcutaneously. Their introduction into the blood 
produces somewhat different results — results that resemble the effects 
•of living bacilli. The first effect of the bacilli is to cause a prolifera- 
tion of the connective tissue cells, which, however, soon degenerate. 
Secondarily, leukocytes are attracted. Aside from the chemotactic 
substance in the dead bacilli, the necrotic cells also yield chemo- 
tactic principles. The substance causing the necrosis is probably 
not the same as the chemotactic substance, since necrosis is present 
even when leukocytes are absent. Most tubercles, but not all, are 
avascular. The necrotic changes also occur when the tubercles 
are small and vascular, as at times in tubercles of the renal glomer- 
uli. In necrotic areas the tubercle bacilli are not healthy, but 
show evidences of degeneration. 

The tubercle bacilli are carried in the body by the lymph or 
blood-stream, or by phagocytes, the carrying cells being them- 
selves killed. Tubercles may be healed by the formation of a 
capsule around them, but they may later break down again. 1 

Koch, in some very important experiments, found that tuber- 
culosis could be cured in guinea-pigs by reinoculating them with 
tubercle bacilli, or by injecting a 50 per-cent. glycerin extract of a 
culture destroyed by heat (tuberculin). The active substance of 
this extract is an albuminous body, which is soluble in glycerin, but 



For the histology of the tubercle, see " Notes on Pathology," p. 70. 



SYPHILIS. 35 

insoluble in absolute alcohol. It does not act directly on the 
bacteria, but destroys the tuberculous tissues, and the bacilli perish 
afterwards from lack of nourishment. 

Tuberculin is prepared as follows : Flasks are partly filled with 
bouillon containing 6 per-cent. of glycerin, and are inoculated on 
the surface of the medium with pure cultures in blood serum or 
glycerin agar. They are then placed in an oven for several weeks. 
The bouillon is finally evaporated on a water-bath to one-tenth the 
original bulk, and the liquid filtered through porcelain. 

SYPHILIS. 

Lustgarten has described a micro-organism which is found 
within the cells of syphilitic lesions. The following stain is recom- 
mended : 

1. Stain the section in anilin-water-gentian 12 to 24 hours at 
the room temperature, or 2 hours at 40 C. 

2. Wash a few minutes in absolute alcohol. 

3. Immerse for 10 seconds in 1.5 per-cent. solution of potassium 
permanganate. 

4. Place in an aqueous solution of sulphurous acid, 1 to 2 
seconds. 

5. Wash in water. 

6. Dehydrate in alcohol. 

7. Clear in oil of cloves. 

Cover-glass preparations are treated in the same way, except 
that the distilled water is used instead of absolute alcohol for de- 
colorizing in step 2. 

In another method the cover-glasses are immersed in hot 
anilin-water-fuchsin for a few minutes (sections in same solution, 
but cold, for 24 hours). They are then placed, first in a weak, 
then in a strong solution of iron chlorid. The covers are washed 
in water, dried and mounted ; sections are rinsed in alcohol, dehy- 
drated, cleared, and mounted. 

The bacilli are not always found in syphilitic lesions, nor are 
they easily demonstrated. 

A micro-organism occurs in the smegma of healthy individuals, 
which is identical in morphology and staining peculiarities with 
Lustgarten's bacillus. 

As the bacilli of tuberculosis and leprosy can be stained by 
the same process, it is possible that the few cases in which the 



36 NOTES ON BACTERIOLOGY. 

syphilis bacillus has been found in the viscera were cases of mixed 
infection. The bacillus has never been isolated nor cultivated, and 
its relation to syphilis must be determined by future experimentation. 

ACTINOMYCOSIS. 

This disease is almost peculiar to the bovine species, the lesions 
being found in the jaw and tongue of the animal. It is due to the 
ray-fungus, or actinomyces, which can be detected by the naked 
eye. Under the microscope it has a rosette shape, and consists 
(a) of a granular central substance containing small round bodies 
(spores) ; (J?) of radiating mycelial threads extending outward and 
terminating in (c) a zone of club-shaped forms. 

Formerly the organism was classed among the pleomorphous 
bacteria, in the genus cladothrix, but recent researches have shown 
that it is a bacillus, the round bodies in the centre being spores, the 
mycelial threads perfect individuals, and the club-shaped bodies 
involution forms. The actinomyces stains well by Gram's method, 
and, better probably, by Weigert's fibrin method. 

It grows upon artificial media, but produces the rosette shape 
only in the body, not in cultures. Introduced into the abdomen of 
rabbits, typical nodules develop in the peritoneum, mesentery, and 
omentum, and show the ray-like arrangement. Infection occurs 
usually through grain, particularly barley. 

GLANDERS. 

The cause of glanders is the bacillus mallei discovered by 
Loffler, in 1882. It is a bacillus with rounded ends, shorter and 
thicker than the tubercle bacillus, non-motile, and non-flagellated. 
Spores have not been demonstrated, although the bacillus can live 
for a time in the dry state. It always occurs as a parasite. 

The disease affects chiefly horses and asses, but is communi- 
cable to man. The guinea-pig and field-mouse are especially sus- 
ceptible to experimental inoculation, while house-mice, white rats, 
and white mice are immune. 

The purulent discharges from the nostrils of horses contain 
but few bacilli and are greatly contaminated with other bacteria. To 
obtain a pure culture, a guinea-pig is inoculated subcutaneously 
with the discharge from a case. The animal dies in 4 to 5 weeks, 
and a pure culture can then be obtained from the lymphatic glands 
or the testicles. 



TETANUS. 37 

The bacillus grows best on glycerin agar or in blood serum, 
at the body temperature. On potato, at incubator temperature, the 
growth is characteristic, appearing, at the end of 48 hours, in the 
form of yellowish, transparent, honey-like drops. Later the trans- 
parency disappears and the amber color changes to a reddish-brown. 
After 4 or 5 weeks' cultivation the bacillus loses its virulence. 

Staining. It does not stain by Gram's method ; the best stain 
is that devised by Kuhne. The sections are placed for 30 minutes 
in a solution of methyl-blue 1.5, alcohol 10, and 5 per-cent. watery 
solution carbolic acid 90. They are then washed in water, and 
carefully decolorized in a solution of HC1 10 drops to 500 c. c. of 
water. They are now at once immersed in a solution of lithium 
carbonate (saturated solution lithium carbonate 8 drops, water 10 
c. c), and then placed in distilled water for a few minutes. After- 
ward they are dipped in absolute alcohol colored with methyl-blue, 
dehydrated in anilin oil colored with a little of the blue dye, then 
washed in the clear oil, then in ethereal oil, and finally cleared in 
xylol and mounted. 

The bacilli are not easily stained, as they give up the stain 
readily when the tissue is decolorized. 

The position of the bacillus in the glander nodules resembles 
that occupied by the tubercle bacillus in the tubercles. The nodules 
are composed chiefly of leukocytes ; the center rapidly degenerates, 
and suppurates, leaving an irregular, ragged-edged ulcer discharg- 
ing an abundant amount of pus. 

There is no immunity to the disease. White rats, though 
immune naturally, become susceptible after glycosuria has been 
produced by feeding the animals with phloridzin. 

Mallein, a glycerin extract of cultures of the glanders bacillus, 
has been separated in about the same way as tuberculin is obtained. 
When injected into animals suffering from the disease, a febrile 
reaction analogous to that following a tuberculin injection in tuber- 
culous individuals, is produced. The substance is used only for 
diagnostic purposes. 

TETANUS. 

The tetanus bacillus is an organism, the most striking feature 
of which is the enlargement of one end produced by a bright spore. 
It stains readily by the anilin dyes and also by Gram's method. Its 
habitat is garden earth, dust, manure, and it is sometimes found in 
the intestinal discharges of animals. 



38 NOTES ON BACTERIOLOGY. 

Isolation and cultivation are difficult, as it will not grow where 
oxygen is present. The spores are very resistant, and the bacillus 
may be isolated by heating the material to be investigated to 8o° C. 
for an hour. In this time all the bacteria are killed and most of 
the spores except those of tetanus. The bacilli are also very resist- 
ant to disinfectants, being able to withstand a 5 per-cent. carbolic 
acid solution for 10 hours and one of mercuric chlorid 1 to 1000 for 
3 hours. The micro-organism grows on all media and gives off a 
characteristic odor. Upon gelatin the colonies at first appear like 
those of the hay bacillus ; but later liquefaction takes place. 

The bacilli usually enter the body from the soil through a 
wound, which may be quite small. The period of incubation is 
often of considerable length, being in man at times 3 weeks. 

Men, horses, mice, rabbits, and guinea-pigs are susceptible ; 
dogs are much less susceptible, while amphibians and most birds 
are immune. The bacilli remain at the seat of inoculation and 
never enter the blood or lymph. In most cases there is a mixed 
infection, the other bacteria using up the oxygen and thus aiding 
in the growth of the tetanus bacillus. The symptoms are due to a 
poison elaborated by the tetanus organism. 

When bacilli, freed from poison, are introduced into the body, 
they fail to produce any sign of the disease, being at once killed by 
the phagocytes. When introduced with the poison or when the 
tissues are simultaneously injured by chemical agents (as lactic 
acid), the toxin which causes the characteristic symptoms is 
deveLoped. The amount of poison generated in the body is 
probably small, but extremely virulent, and rapidly produced. 
Kitasato found that excision or cauterization of the point of in- 
oculation in mice failed to save the animal unless practiced within 
an hour after inoculation. 

Post-mortem examination shows the organs to be normal in 
appearance except the nervous system, in which there is congestion. 

The existence of the toxin has been demonstrated in the blood 
and urine of diseased animals. The toxin can easily be prepared 
from cultures outside the body. It is destroyed by exposure to 
light or by heating to from 6o° to 65 ° C. An antitoxin can be 
produced in the blood serum of horses, goats, and dogs by the 
gradual introduction of the toxin, as is done in diphtheria. The 
antitoxin is obtained in solid form by precipitating the serum with 
alcohol. 



ANTHRAX. 39 

ANTHRAX. 

Anthrax, or splenic fever, is not common in this country or in 
England, but is a frequent and dreaded disease on the European 
continent. Cows and sheep are most often affected. Among 
laboratory animals, white mice, guinea-pigs, and rabbits are very 
susceptible, while dogs, most birds, and amphibians are almost 
immune. Man is but slightly susceptible, the disease usually being 
local — malignant carbuncle or pustule ; general infection is rare. 
The cause of the disease is the bacillus of anthrax. 

Anthrax bacilli are large, rectangular rods, 5 to 20j* in length 
and 1 to 1.25^ in width, and have a tendency to arrange themselves 
in long threads. They form oval central spores, are non-motile, 
and have no flagella. They stain readily with the watery solutions 
of the anilin dyes and by Gram's method. In sections, picro-carmin, 
followed by Gram's method, gives a beautiful picture. The spores 
can be stained with carbol-fuchsin, the bacilli being decolorized 
with a weak acid, and then counterstained with methyl-blue. 

On the surface of gelatin plate cultures the colonies appear as 
minute, round, whitish dots, liquefying the gelatin as they increase 
in size. Under the microscope they present a tangled center, from 
which large numbers of curls extend, each composed of parallel 
threads of bacilli. The colonies make beautiful adhesive or impres- 
sion preparations. In gelatin puncture cultures the bacilli grow 
most luxuriantly on the surface where oxygen is plentiful. As the 
growth progresses, fine filaments extend from the puncture out into 
the gelatin, giving the culture an appearance of an inverted ever- 
green tree. Eventually the entire gelatin is liquefied, and the 
growth precipitates. On agar the growth has few characteristics. 
On the potato a creamy-white layer is produced ; sporulation is 
marked. Blood-serum cultures lack peculiarities ; the medium is 
slowly liquefied. 

The bacillus grows between the extremes of 20 and 45 ° C., 
best at 37 C. An exposure to a temperature of 42 ° or 43 ° C. for 
24 hours destroys its virulence. 

The anthrax bacillus is a parasitic organism, but by reason of 
its spore formation, it can exist in this latent form outside of the 
animal body until appropriate conditions for its development are 
presented. Ordinarily infection takes place through the respiratory 
or the intestinal tract. Men coming in contact with diseased cattle 
may be inoculated with the germ through a wound, and develop 



4o NOTES ON BACTERIOLOGY. 

malignant pustule, which may prove fatal. Those who work with 
the skins and hair of animals dead of anthrax sometimes suffer 
from a pulmonary form of the disease, " wool-sorters' disease," 
caused by the inhalation of spores attached to the wool. 

In the laboratory the method of inoculation is to cut away a 
little of the hair from the abdomen of a guinea-pig or rabbit, or the 
root of a mouse's tail, make a little pocket with a snip of a pair of 
sterile scissors, and introduce the virus from a pure culture on a 
heavy platinum wire, the end of which is flattened, pointed, and per- 
forated. The animal dies in from 24 hours to 3 days, according to 
the species. At the autopsy the naked eye changes are not 
marked. When a microscopic examination is made of the tissues, 
the capillaries are found to be filled with immense numbers of bacilli. 

The inoculation of bacilli, the virulence of which has been 
reduced by growing them under unfavorable conditions, is capable 
of rendering cows and sheep immune to anthrax subcutaneously 
inoculated, although such vaccinated animals are not perfectly pro- 
tected against intestinal anthrax. Immunity can also be secured by 
introducing simultaneously with anthrax another bacterium not at 
all related to anthrax. 

At one time a discussion was waged how the pastures from 
which cattle acquired the disease became infected. It has now been 
pretty conclusively shown that infection is by the discharges — 
urine and feces — of diseased animals ; hence the importance of the 
prompt destruction, by burning or by deep burial, of all infected 
animals. 

MALIGNANT EDEMA. 

This is due to a large slender bacillus, often found to contami- 
nate cultures of the tetanus bacillus ; it is almost as large as anthrax^ 
but with rounded ends, and motile by virtue of a number of flagella 
attached to its ends and sides. It is strictly anaerobic, grows well 
at the temperature of the room and the incubator, and produces 
oval central spores. Its habitat is garden earth, but it is also found 
in dust, in the wash water from houses, and sometimes in the 
intestines of animals. It is pathogenic to most of the lower animals 
except cattle. Inoculation should be made subcutaneously, into a 
pocket of the skin, as when deposited on a surface abrasion, 
the presence of oxygen interferes with the development of the 
organisms. If the animal is a mouse, guinea-pig, or rabbit, it 



DIPHTHERIA. 4 1 

usually dies in 48 hours, the autopsy revealing a general subcuta- 
neous edema, containing immense numbers of the bacilli. In the 
blood the bacilli are few or cannot be found on account of the 
presence of oxygen. 

Two cases of infection in man are reported ; both were typhoid 
fever patients who had been injected with musk, to which the 
organisms were probably adherent. 

The bacillus stains well with the ordinary dyes, but not by 
Gram's method. Pure cultures are readily obtained, best from the 
edematous tissues of rabbits or guinea-pigs inoculated with garden 
earth. 

DIPHTHERIA. 

This disease is due to the Klebs-Loffler bacillus, discovered by 
Klebs in 1883. It is about the length of the tubercle bacillus, but 
twice the diameter, and has rounded ends. One of its striking 
peculiarities is its irregularity in size and shape. It is very probable 
that the markedly irregular individuals represent involution forms, 
since they are far more plentiful in old than in new cultures. The 
bacilli stain with the ordinary stains, but best with Loffler's alkaline 
methyl-blue solution (see page 17). In tissues they are best stained 
by Gram's method or by Weigert's fibrin stain. 

The organisms are optionally anaerobic, do not form spores and 
are readily killed by heat (50 to 5 8° C), but withstand drying for 
several weeks. Flagella have not been demonstrated. They grow 
on all media, but most rapidly on Loffler's mixture : Blood serum 
3 parts, meat-bouillon, containing 1 per-cent. of glucose, 1 part. 
On this medium, when kept at 37 ° C, growth occurs in the form 
of white colonies at the end of 12 hours. Few bacteria grow so 
rapidly, and scarcely any that are found in the throat. Gelatin is 
not liquefied by the organism. Milk is a good culture medium and 
may be a means of transmission of the infection. In litmus milk 
the alkaline reaction is replaced by an acid reaction, but as the 
culture grows old, the medium becomes again alkaline. 

In man diphtheria is a local disease, the bacilli being only 
found in the membrane, and the general symptoms result from the 
absorption of poisons produced by the bacillus. In animals 
injected with the virus, the lesions differ from those noted in man. 
If 0.5 c. c. of a bouillon culture, 24 hours old, is injected into a 
susceptible animal (guinea-pig, kitten, or pup), a fibrinous exudate 



42 NOTES ON BACTERIOLOGY. 

and an extensive edema develop at the point of inoculation. The 
animal dies in from 24 to 36 hours, the organs, especially the liver, 
presenting at the autopsy minute white areas of necrosis. In these 
areas the bacilli are not found. Similar lesions are seen in other 
infections. The lymphatic glands and the adrenals are enlarged, 
the latter being also hemorrhagic. Rarely the bacilli are present 
in the internal organs and the blood. When introduced into the 
trachea of animals the bacillus produces a false membrane as in 
man. 

The pseudo diphtheria bacillus resembles the true diphtheria 
bacillus very closely, and is probably merely an attenuated form of 
the latter. It is a little shorter when grown on blood serum, grows 
more rapidly in bouillon at from 20 to 22° C, and is not patho- 
genic to the lower animals. 

In the human throat virulent bacilli have been found as late as 
five weeks after the disappearance of the membrane. 

A toxin can be separated from cultures of the organisms by 
filtration through a porcelain filter, and can be obtained in such 
concentration that 0.1 c. c. will kill a guinea-pig in from 24 to 30 
hours. Animals can be rendered immune to the bacteria or the 
toxin — in the blood serum of such animals an antitoxin is found. 

Preparation of the toxin. The most virulent bacilli obtainable 
are grown in Loffler's mixture at 37 C. for 3 or 4 weeks, the 
medium being in a thin layer and exposed to a constant stream of 
moist air. The material is then filtered through porcelain. The 
filtrate should possess such a toxic power that 0.1 c. c. will kill a 
guinea-pig weighing 500 grams, in from 24 to 36 hours. 

Immunization of animals. For practical purpose the horse is 
the best animal. The first injection is 1 c. c. At intervals of 8 
days larger and larger doses are introduced, until finally as much 
as 300 c. c. are injected. As the toxin causes some local reaction, 
the injections should not be made until that has disappeared. If 
the injections are made too rapidly in succession, the animal is apt 
to die of cachexia. 

Preparation of the serum. The horse is bled and the blood 
received in sterile bottles and allowed to coagulate in the cold. 
The serum is pipetted off, and preserved from decomposition by 
the addition of camphor, phenol, or trikresol. The serum should 
protect an animal against ten times the amount of toxin ; i. e. } 
0.01 c. c. antitoxin should neutralize 0.1 of toxin. The strength of 



CHOLERA. 43 

the serum is expressed in " immunity units " — an immunity unit 
being the amount of antitoxic serum required to protect a 500 
gram guinea-pig against ten times the minimum fatal dose of toxin. 

CHOLERA. 

The cause of cholera is a spirillum discovered by Koch in 
1884. It is short, about half the length of the tubercle bacillus, 
considerably stouter, and distinctly curved on itself, hence the 
name " comma bacillus." When the conditions of nutrition are 
unfavorable, so that division is not rapid, long, winding, spiral threads 
are formed, showing that the organism is a spirillum. The bacteria 
are actively motile by reason of a flagellum projecting from one 
end. Involution forms are common in old cultures and sometimes 
also in fresh ones, the germs from different sources varying in this 
respect. Spores have not been found by most observers. The 
spirillum has but little resisting power, although it multiplies with 
great rapidity under favorable circumstances. It is readily killed 
by germicides, by a temperature of 55 C, and by drying, although 
in the moist state it retains its vitality for months. Staining is 
readily accomplished with the ordinary anilin dyes, best perhaps 
with a weak aqueous solution of fuchsin ; it is not stained by 
Gram's method. In making a cover-glass preparation from the 
intestinal discharges, one of the rice-like bodies is smeared on the 
glass and stained in the customary manner. 

Cultures. On gelatin-plates the organism produces highly 
characteristic colonies. The gelatin is slowly liquefied and as the 
liquid gradually evaporates, the colonies seem to be situated in little 
pits with sloping sides, the plate appearing to be full of air bubbles. 
The colonies are not regular in contour, and those which have not 
yet reached the surface are coarsely granular and yellowish in color. 
As they increase in size they present a powdered-glass appearance. 
The growth scarcely resembles that of any other micro-organism. 
In puncture culture the growth occurs along the entire stab, but best 
at the surface, where liquefaction and evaporation take place so that 
a funnel-shaped depression is produced. The growth reaches the 
sides of the tube in from 5 to 7 days. In 8 weeks the germs die 
and cannot be transplanted. 

On agar the growth is not peculiar, but the vitality is retained 
much longer. The blood serum culture offers nothing peculiar. 
On potato the growth is active, even when the medium is acid. In 



44 



NOTES ON BACTERIOLOGY. 



bouillon-peptone solution the organisms grow well and produce a 
wrinkled mycoderma on the surface, the fluid below remaining 
clear. They grow well in milk without causing any visible change, 
but die as soon as the medium becomes acid. In sterilized water 
they develop with great rapidity and remain alive for months. In 
unsterilized water they are soon destroyed by other bacteria. 

One of the characteristics of the bacterium is its ability to pro- 
duce indol simultaneously with nitrites. The simple addition of a 
few drops of H 2 S0 4 suffices to produce a red color — the indol 
reaction. The organism also develops certain toxic substances 
which have been isolated. 

The cholera spirillum is always found in the evacuations of 
cholera patients, sometimes in drinking water, in milk, and in foods 
moistened with infected water. They enter the body with the 
food and drink. 

Animals do not suffer from a disease similar to cholera during 
epidemics, nor does the administration of food to which cholera 
discharges or cultures are added, produce the disease in them. 
Hypodermic injections are also without consequences. When, 
however, the gastric juice of a guinea-pig is neutralized with sodium 
carbonate and peristalsis is checked with opium, the introduction of 
a cholera culture kills the animal in 48 hours. The autopsy shows 
the intestines congested and filled with a rice-water fluid rich in 
bacilli, a condition like that found in man. 

In man and animals the bacteria are found only in the intestines, 
where they enter the epithelial cells and basement membrane, aiding 
in the detachment of the cells. They are never found in the other 
organs or in the blood. 

Their detection in drinking water is difficult. Loffler recom- 
mends the addition of 200 c. c. of water to 10 c. c. bouillon, allowing 
the mixture to stand in the incubator 12 to 24 hours, and then 
making plate cultures from the surface, where development is most 
rapid because of the presence of air. 



THE FINKLER-PRIOR SPIRILLUM. 

This was obtained from a case of cholera nostras in 1884, and 
closely resembles the cholera spirillum morphologically, but differs 
in its mode of growth, particularly on gelatin and potato. On 
gelatin plates the colonies are situated in slight depressions, are 
yellowish-brown, and finely granular, but are surrounded by a zone 



THE SPIRILLUM OF DENECKE AND GAMALEIA. 45 

of liquefied gelatin. In puncture culture a more extensive and 
rapid liquefaction occurs — along the entire stab. The absence of 
the air-bubble and the cloudy nature of the liquefied medium 
are additional points of differentiation from the cholera germ. It 
does not produce indol. 

The organism grows readily, but without peculiarity, on blood 
serum and agar. In milk or water it does not grow well. It stains 
readily with all ordinary dyes, especially with fuchsin. Injected 
into the stomach of guinea-pigs treated after Koch's method, 30 
per-cent. of the animals die, but the intestinal lesions are not the 
same as in cholera. The spirillum is probably a frequent and harm- 
less inhabitant of the human intestine. 

THE SPIRILLUM OF DENECKE. 

This occurs in old cheese, and resembles the cholera spirillum 
in form and staining properties. On gelatin-plates it grows more 
rapidly than the cholera germ, but more slowly than the Finkler- 
Prior spirillum. The colonies differ from cholera in the rapid 
liquefaction, rapid growth, yellow color, irregular form, and distinct 
lines of circumscription which surround the colonies. Indol is 
produced at times, but not constantly. 

It is not pathogenic, and probably never associated with dis- 
ease in man, and is only mentioned because of its morphological 
relations to the cholera spirillum. 

THE SPIRILLUM OF GAMALEIA (VIBRIO 
METSCHNIKOVI). 

The organism is closely related to the cholera spirillum, and 
was first obtained from the intestines of chickens affected with a 
disease similar to chicken cholera. It is a trifle shorter and thicker 
than the spirillum of cholera, has also rounded ends, is motile, 
having a terminal flagellum. It grows well at ordinary tempera- 
tures and at that of the incubator. The ends stain more deeply 
than the center ; it does not stain by Gram's method. 

Upon gelatin plates the colonies present a marked similarity to 
those of true cholera, but liquefaction is quite rapid and gives rise 
to the presence of a turbid fluid in the concavity. Generally a 
few colonies will be found which resemble the cholera germ by 
occupying small conical depressions. Under a high power the 
contents of the colonies are found to be in active motion. In 



46 NOTES ON BACTERIOLOGY. 

gelatin tubes the culture is very much like that of the cholera 
spirillum, but develops more slowly. Upon agar a yellowish-brown 
growth develops along the whole line of inoculation. No growth 
occurs on potato at the room temperature, but in the incubator a 
yellowish-brown or chocolate-colored growth takes place. In 
bouillon the growth which occurs at the incubator temperature is 
quite characteristic and very different from that of the cholera 
spirillum. The medium becomes cloudy throughout, of a grayish- 
white color, and opaque. A folded and wrinkled mycoderma forms 
upon the surface. 

The addition of sulphuric acid develops the indol reaction. 

The organism is pathogenic for animals (chickens, pigeons, 
guinea-pigs), but not for man. 

CHICKEN CHOLERA. 

Chicken cholera is a very fatal epidemic disease, which affects 
chickens, ducks, and geese, and causes a profuse serous diarrhea. 
The bacteria which have been found to cause the disease are 
short, broad bacilli with rounded ends, non-motile, without spores, 
and do not stain by Gram's method. The organism appears to be 
identical with the bacillus of rabbit septicemia, the bacillus of swine 
plague, and several others bearing different names. 

The bacillus of hog cholera resembles it very closely, but differs 
in being motile, and in producing a straw-colored growth on potato. 

TYPHOID FEVER. 

This is caused by a short, actively-motile bacillus, i to 3^ long 
and .5 to .8ft wide, with rounded ends. The motility is due to the 
presence of numerous flagella which project from the sides. The 
organism stains with the ordinary dyes, but best with Loffler's solu- 
tion ; it is not colored by Gram's method, and in tissues stains with 
difficulty, as it gives up the stain very readily. The bacillus is 
much more resistant than most pathogenic bacteria, and can live 
both as a saprophyte and as a parasite. 

It has been found in water, air, on soiled clothing, in dust and 
sewage, in milk, and on vegetables sprinkled with water. In a 
number of instances the disease was traced to the contamination of 
oysters with the bacteria. The bacilli are killed at 6o° C, but 
resist freezing and thawing several times repeated. They have 
been found alive in linen for from 60 to 72 days, and are known to 



TYPHOID FEVER. 47 

retain their vitality when buried in the upper layers of the soil for 
nearly six months. They can live a long time in distilled water, 
but in ordinary water are overcome by more vigorous organisms in 
a few days. The bacillus will grow in media containing as much 
as o.i or 0.2 per-cent. of carbolic acid. 

Pure cultures may be obtained from the stools of typhoid fever 
patients by inoculating gelatin tubes containing 0.05 per-cent. of 
carbolic acid, and making plates. The carbolic acid prevents the 
growth of the majority of organisms except the typhoid bacillus 
and the bacillus coli communis. 

The typhoid bacillus does not liquefy gelatin, and its colonies 
on this medium, as well as upon agar and blood serum, are not 
characteristic. The growth on potato is peculiar, and will be found 
described in the table below. 

The isolation of the bacillus is difficult on account of the close 
resemblance between it and the bacillus coli communis, which is 
constantly present in the intestines. It is similar to the typhoid 
bacillus in morphology, and grows in the same manner on gelatin, 
agar, blood serum, and bouillon. The similarity is so great that 
some claim the two bacilli are identical. The following table 
presents the differences between them : 

Bacillus of Typhoid Fever. Bacillus Coli Communis. 

1. Does not produce gas. 1. Produces gas in media containing glu- 

cose. 

2. On acid potato produces an invisible 2. On acid potato gives rise to a smeary, 

growth. (At times growth is yel- elevated, circumscribed, brownish 

lowish or brownish). layer, resembling that of typhoid on 

alkaline or neutral potato. 

3. Does not coagulate milk, though pro- 3. Produces a marked acidity, and coagu- 

ducing a slight acidity. lates milk. 

4. Does not produce indol. 4. Produces indol. 

The typhoid bacilli enter the body through the mouth, and 
passing the acid gastric juice uninjured, settle in the solitary glands 
and Peyer's patches of the intestines. The period of incubation is 
from 1 to 3 weeks. The organisms induce primarily a hyperplasia 
of the lymphoid structures, then a necrosis and sloughing. They 
can be found in the intestinal lesions, in the mesenteric glands, in 
the spleen and liver, in the kidneys, and in any other local lesions 
that may be present. Ordinarily they are not demonstrable in 
the blood, but at times have been found in that obtained from the 



48 



NOTES ON BACTERIOLOGY. 



rose-colored spots. The local lesions are slight in comparison 
with the constitutional symptoms, which are now known to be due 
to a toxalbumin elaborated by the organisms. 

Patients at times die with the clinical picture of typhoid fever^ 
but do not show the characteristic lesions ; the diagnosis of typhoid 
fever has been confirmed in these cases by the discovery of the 
typhoid bacilli in the spleen. 

The demonstration of the bacilli in the spleen is often difficult. 
It is therefore advisable to wrap the organ in a towel impregnated 
with bichlorid of mercury and place it in a warm room for 3 days, 
which permits the organisms to develop actively. 

Typhoid fever is communicated to animals with great difficulty 
— they are not affected when their food is mixed with fecal 
discharges containing the bacilli or with pure cultures. Injections 
of pure cultures into the peritoneal cavity are without effect, except 
in the case of mice and rabbits, which die and show the bacilli in 
the blood in large numbers. In animals which were manipulated 
after the method of producing cholera, intestinal lesions resembling 
those seen in man were observed. 

An antitoxin for clinical use has not been produced. Animals 
are easily accustomed to the organism, and seem to develop some 
antitoxic substance in their blood serum. Good results have been 
obtained in a few cases by the hypodermic injection of sterilized 
cultures of the bacillus pyocyaneus. 

RELAPSING FEVER. 



In 1873 Obermeyer discovered in the blood of patients suffer- 
ing from relapsing fever a spirillum 20 to 40^ in length and o.i/i in 
width. The spirilla are long, slender, have pointed ends, are 
flexible, and move vigorously by means of flagella. They stain 
readily with the ordinary dyes, but not by Gram's method. The 
spirillum appears to be a true parasite, and has never been culti- 
vated artificially. There is no doubt as to its pathogenic power; 
it is constantly present, and the disease can be reproduced in man 
and monkeys by injecting the blood of patients suffering from 
relapsing fever. 

During the febrile period the organisms are numerous in the 
blood, and move actively both by rotation on their long axis and by 
undulation. At the crisis they are motionless, and most of them 



INFLUENZA. 49 

are contained in leukocytes, and are apparently dead. The tend- 
ency of the paroxysms to recur has led to a belief in the existence 
of spores, but they have never been demonstrated. 

INFLUENZA. 

Canon and PfeifTer, in 1892, discovered, simultaneously, a bac- 
terium which they look upon as the cause of influenza, and which 
they found in the blood and in the bronchial discharges. It is a 
very small bacillus, 0.5^ in lengths, and occurs usually singly, but 
may form chains, and stains poorly, even with dyes like carbol- 
fuchsin or Loffler's alkaline methylene-blue solution. One of the 
best stains is the following : 

Concentrated watery solution methyl-blue 40 

. 0.5 per-cent. solution eosin in 70 per-cent. alcohol 20 

Distilled water 40 

A cover-glass spread with blood is dried, fixed by a 5 minutes' 
immersion in absolute alcohol, and stained in the solution for from 
3 to 6 hours ; then it is washed in water, dried, and mounted in 
balsam. The bacilli are stained blue, and are at times abundant, at 
others but few are present. They are often enclosed in leukocytes. 
They do not stain by Gram's method. 

The organism is non-motile and, as far as known, does not 
form spores. It speedily succumbs to drying, and is killed by a 5 
minutes' exposure to a temperature of 60 ° C. Below 28 ° C. it will 
not grow. 

Cultures. It does not grow on gelatin or plain agar. On 
glycerin agar, left in the incubator, minute, colorless, transparent, 
drop-like colonies develop along the line of inoculation in 24 hours. 
They resemble condensed moisture, never become confluent, and 
are so small that they cannot be detected without a lens. On 
bouillon a scant development occurs, appearing as whitish particles 
on the surface and subsequently sinking to the bottom. 

The bacillus grows well on culture media containing hemo- 
globin or blood, and can be repeatedly transplanted without losing its 
vitality. It has not been positively demonstrated that it is the cause 
of influenza, but it has been shown that it is constantly present in 
all uncomplicated cases of influenza, and only in influenza, and can 
be found as long as the purulent secretion continues ; then it dis- 
appears. 

4 



5o 



NOTES ON BACTERIOLOGY. 



MEASLES. 

Canon and Pielicke, in 1892, discovered in the blood of measles 
patients an organism varying in size and shape, sometimes resem- 
bling a diplococcus, at others appearing as a bacillus as great in 
length as the diameter of a red corpuscle. The discoverers employ 
the following method of staining. The blood is spread thinly upon 
a cover-glass and fixed by 5 to 10 minutes' immersion in absolute 
alcohol. The cover-glass is then placed in a solution of 

Concentrated aqueous solution methyl-blue 40 

0.25 per-cent. solution of eosin in 70 per-cent. alcohol ... 20 
Distilled water 40 

and stood in the incubator at 27 C. for from 6 to 24 hours. The 
bacilli do not stain uniformly ; they also do not stain by Gram's 
method. 

They were found not only in the blood, but also in the secre- 
tions from the nose and eyes ; they are said to persist throughout 
the course of the disease. 



PNEUMONIA. 
I. Lobar or Croupous Pneumonia. 

The pneumococcus of Frankel and Weichselbaum is found in 
at least 75 per-cent. of cases of lobar pneumonia. Discovered by 
Steinberg in 1880, in his own saliva, and also by Pasteur in saliva in 
the same year, its relation to pneumonia was not revealed until 
nearly five years later. 

In its typical form it is lanceolate in shape, but its morphology 
is variable. In bouillon it occurs in pairs or chains, so that some 
have been disposed to look upon it as a streptococcus. In the 
fibrinous exudate of croupous pneumonia, in the rusty sputum, 
and in the blood of rabbits and mice that have been inoculated, 
they have a distinct lanceolate shape, and occur in pairs, the pointed 
ends being approximated, and are surrounded by a distinct, clear 
halo, or capsule, which is thought by some to be a swollen cell 
wall, by others a mucus-like secretion given off by the organism. 
When grown on the ordinary solid media, the capsules are absent. 
It has no motion, is without spores, and is unable to resist any 
unfavorable conditions when grown artificially. It stains well with 
the ordinary dyes, and very beautifully by Gram's method. 



PNEUMONIA. 51 

The pneumococcus is found normally in the saliva of some 
persons ; and when such saliva is injected into rabbits, the latter 
die of septicemia, the bacteria occurring abundantly in the blood 
and tissues. 

Pure cultures can be obtained by inoculating rabbits with saliva 
and recovering the organism from the blood, or from the rusty 
sputum of pneumonia by the method by which tubercle bacilli are 
cultivated from tuberculous sputum. 

The organisms lose their virulence in culture media in a few 
days, and, unless continually transplanted, die in one or two weeks. 
Its growth on gelatin is slow, and the medium is not liquefied. On 
agar and on blood serum minute, transparent, scarcely visible 
colonies develop. In bouillon the growth is active, the medium 
becoming clouded. In milk the growth is also active and produces 
coagulation ; no growth occurs on potato. 

To maintain the virulence of the micro-organism, it is neces- 
sary to pass it frequently through the bodies of susceptible animals. 

When a pure culture or a piece of pneumonic lung is intro- 
duced into a mouse, guinea-pig, or rabbit, the animal dies in from 
I to 2 days of general septicemia. At the point of inoculation there 
is an inflammatory edema. The spleen is enlarged, reddish-brown, 
and firm. The blood contains large numbers of the organisms with 
distinct capsules. The lungs show no pneumonic change. Even it 
the injection is made directly into the lung tissue, pneumonia is not 
produced. 

Pneumonia is said, however, to have followed the introduction 
of the bacteria into the trachea of animals. 

Unfortunately the name pneumococcus has been applied to a 
micro-organism very different from that just described. It was dis- 
covered by Friedlander, in 1883, in the exudate in croupous pneu- 
monia, and being thought by its discoverer to be the cause of the 
disease, was called the pneumococcus, or more properly the pneumo- 
bacillus. 

The two micro-organisms are, however, often confounded. 
That of Friedlander is distinctly a bacillus, but sometimes closely 
resembles the pneumococcus, often forming chains of four or more 
elements, and is also commonly surrounded by a transparent 
capsule. It is non-motile, has no spores and no flagella, and stains 
by the ordinary dyes, but does not stain by Grmrfs method. 

In cultures great differences exist between the two organisms. 



52 NOTES ON BACTERIOLOGY. 

Friedlander's pneumobacillus forms distinct colonies on plates 
in 24 hours, and produces a luxuriant growth in puncture cultures. 
It will also grow at a lower temperature than the pneumococcus — 
at 1 6° C. On the surface of agar or blood serum it gives a distinct 
growth, and also a rapid and abundant growth on potato. 

The only pathogenic results were obtained in the lung and 
pleura of mice. Rabbits and guinea-pigs are immune to it. 

At present it is looked upon as a very feebly pathogenic 
organism, which is generally a harmless saprophyte, but may at 
times produce inflammatory changes in the body. 

II. Catarrhal Pneumonia. 

This is a localized inflammation about the bronchioles, and is 
not due to specific micro-organisms. The most common causes 
are staphylococci and streptococci of suppuration. 

Friedlander's bacillus may also be connected with its pro- 
duction. 

III. Tuberculous Pneumonia. 

At times the tubercle bacilli are distributed to an entire lobe or 
an entire lung. Such a lobar inflammation may be due to the 
tubercle bacillus alone, but more often this 'Organism is aided by 
the staphylococcus, streptococcus, tetragonococcus, pneumococcus, 
pneumobacillus, or other bacteria. 

IV. Mixed Pneumonia. 

Often pneumonia occurs during or shortly after influenza. In 
these cases the influenza bacillus and the pneumococcus are as a 
rule present together. Sometimes the pneumococcus and the 
staphylococcus operate simultaneously, purulent 'pneumonia with 
abscess formation being the consequence. 

Almost any combination of bacteria is possible in the lungs. 

GONORRHEA. 
The cause of gonorrhea is the gonococcus of Neisser (1879). 
It is a coccus arranged in pairs, sometimes in fours. The approxi- 
mated surfaces of the pairs are concave. The organism is non- 
motile and does not form spores. It stains readily with weak 
aqueous solutions of the anilin dyes, but not by Gram's method. 
In the urethral discharges it is found from the beginning until the 
end of the disease, growing fewer in numbers in the later stages. 



MOUSE SEPTICEMIA. 53 

It is generally found within pus cells or attached to the surface of 
epithelial cells, and should always be searched for as a diagnostic 
feature of gonorrhea. 

The cultivation of the gonococcus is not easy ; it has been 
accomplished on human blood serum. A drop of the pus is mixed 
with the liquid serum and the latter added to an equal part ot 
melted 2 per-cent. agar at 40 C, the mixture being then poured 
into Petri dishes. As soon as the medium is firm, the dishes are 
placed in an incubator at 37 C. Within 24 hours colonies develop, 
having a dark center and a granular periphery. Transferred to 
coagulated human blood serum, the organism develops gray colonies 
which later become confluent. The gonococcus has also been 
grown upon acid gelatin and even in acid urine, where it develops 
on the surface, while the pus cocci that may be present sink 
deeper into the medium. Turro has succeeded in inoculating the 
urethra of dogs with cultures grown on acid gelatin. It was not 
even necessary to produce a lesion of the mucous membrane in 
order to cause the disease. 

The gonococcus is not only constantly present in gonorrhea, 
but is frequently found in the sequelae and complications of that 
disease, endometritis, salpingitis, cystitis, peritonitis, arthritis, con- 
junctivitis, etc. 

The cocci at first grow in the superficial epithelial cells, but 
soon penetrate to the deeper layers. The peri-urethral abscesses at 
times occurring in gonorrhea are generally due to the staphylococcus 
aureus and albus. 

After apparent recovery the gonococci may yet remain latent 
in the urethra and be capable of setting up a relapse. The gono- 
coccus is not easily killed ; it withstands drying very well. 

Bumm has found in the urethra a coccus resembling the gono- 
coccus, and claims that the shape and the position in the cells are 
not positively diagnostic, but that added to these we must have the 
refusal to stain by Gram's method. 

MOUSE SEPTICEMIA. 

The bacillus of mouse septicemia was isolated by Koch in 1878 
from the blood of mice that had died of septicemia induced by the 
injection of putrid blood. The organism is very small, i.oxo.2ft, 
grows well at room and incubator temperatures, and is facultatively 
anaerobic. 



54 NOTES ON BACTERIOLOGY. 

By some observers the bacillus of mouse septicemia is considered 
identical with the bacillus of swine erysipelas. 

Mice die of septicemia in from 40 to 60 hours ; guinea-pigs are 
not susceptible. Swine present paralytic weakness of the hind 
limbs, and die in 2 or 3 days. In all animals the lesions are the 
same — the disease is a septicemia. The bacteria can be found in 
the organs, particularly the lung and spleen, but are few in the 
blood. They stain well by Gram's method. Of the organs, only 
the spleen and the lymphatic glands appear abnormal, being 
enlarged. 

Pasteur, Chamberlain and Roux have secured immunity in 
animals by vaccination, but the vaccinated animals are a source of 
infection, and should be isolated. 

TETRAGENUS. 

This is found in normal saliva, in tuberculous sputum, in 
tuberculous cavities, and sometimes in acute abscesses. It is a 
large micrococcus, ip, in diameter, occurring in groups of four, 
surrounded, in the animal tissues, by a transparent capsule. Gram's 
method serves best for its demonstration in tissues ; it also stains 
well with the ordinary dyes. On gelatin-plates it produces in from 
24 to 48 hours small white colonies which under the microscope 
appear finely granular and lobulated. In gelatin punctures a large 
white surface-growth occurs, but very scant development in the 
puncture. The organism also grows on agar, potato, and blood 
serum. 

White mice rapidly die of tetragenus septicemia when inocu- 
lated with pure cultures or with tuberculous sputum. House mice, 
field mice, dogs, and rabbits are resistant. 

The organism, when associated with others in the human body, 
may hasten tissue necrosis, and contribute to the formation of tuber- 
culous abscesses and cavities ; and it may also be a factor in the 
production of hectic fever. 

SUPPURATION. 

Suppuration is due to a variety of micro-organisms which 
enter into wounds usually from the hands or instruments, rarely 
directly from the atmosphere. The skin is the habitat of a coccus 
— staphylococcus epidermidis albus — which may cause the so-called 
" stitch-abscesses." It is probably an attenuated form of the 



STREPTOCOCCUS PYOGENES. 55 

staphylococcus pyogenes albus. The latter is often present on the 
skin, but is feebly pathogenic to animals. 

The staphylococcus pyogenes aureus is almost constantly present 
on the skin, but only in small numbers ; it is virulent and the most 
common organism of suppuration. It is found in the dust of 
houses and hospitals, especially in surgical wards ; on the skin, in 
the nose, mouth, conjunctiva, and ears. In culture media it occurs 
in masses or evenly distributed. It stains easily, is facultatively 
anaerobic, and grows well on all media, producing an orange- 
yellow pigment. It liquefies gelatin rapidly and coagulates milk. 

Its entrance into the skin causes furuncle or carbuncle. In 
animals the subcutaneous injection produces as a rule abscesses, 
and often a iatal result, the organisms being found in the blood and 
in infarcts in the internal organs. In man it is found in carbuncles, 
abscesses, and furuncles, in osteomyelitis, ulcerative endocarditis, etc. 

The staphylococcus pyogenes citreus is identical with the former, 
except that on agar and potato it produces a lemon-yellow growth. 
It is less common and less important than the other pyogenic 
staphylococci. 

Streptococcus Pyogenes. 

This grows in chains, is non-motile, and does not form spores. 
It stains readily with the ordinary dyes; also by Gram's method. 
On gelatin it forms small colonies, without liquefaction of the 
medium ; on agar and blood serum it produces a slow, pale, trans- 
parent growth; it does not grow on potato. In milk it grows 
readily ; it coagulates and and then digests the medium. It is not 
very pathogenic to lower animals and subcutaneous injections in 
mice and rabbits are usually without effect. Rubbed into a rabbit's 
ear, a patch of erysipelas is produced, which soon disappears. 

In man the organism is found in phlegmonous suppuration, 
ulcerative endocarditis, puerperal endometritis, and at times in the 
throat as the cause of a false membrane like that produced by the 
Klebs-Loffler bacillus. 

The streptococcus pyogenes is believed to be identical with the 
streptococcus of erysipelas. The latter can be obtained in pure 
cultures from the serum secured by puncture of the margin of an 
erysipelatous patch. It is a small coccus forming chains, and 
grows best at a temperature of from 30 to 37 C. Its cultures 
are identical with those of the streptococcus. 



56 



NOTES ON BACTERIOLOGY. 



The fact that malignant tumors when infected with erysipelas, 
sometimes slough and disappear, has led to the use of a toxin pre- 
pared from cultures of the streptococcus of erysipelas for therapeutic 
purposes. Cultures of the organism are grown for 3 weeks ; the 
bouillon is then inoculated with the bacillus prodigiosus, kept at 
room-temperature for 10 or 12 days, and then sterilized by heating 
to from 50 to 6o° C. for an hour. The combined toxin seems 
to give better results than the pure erysipelas toxin. It has been 
employed with some success in sarcoma. 

Bacillus Pyocyaneus. 

This is the bacillus of blue or green pus. It liquefies gelatin 
and gives to it a greenish color. On agar it produces a growth at 
first bright-green, later bluish. It is highly pathogenic to animals, 
but immunity is readily produced. Injected subcutaneously into 
guinea-pigs, it causes a rapidly-forming edema, suppuration, and 
death. Immunity is induced by the injection of sterilized cultures 
(heated to 5 6° C). It is common as a saprophyte. 

Bacillus Pyogenes Fcetidus. 

This gives rise to an offensive odor. It grows on all media, 
producing grayish-white colonies ; it does not liquefy gelatin, and 
is pathogenic for mice and guinea-pigs. 

Besides those named above the bacillus coli communis, the 
bacillus of typhoid fever, and the pneumococcus should be men- 
tioned as occasional pus producers. The first is found in sup- 
puration in the bile-ducts and the appendix ; the last in meningeal 
suppuration. The typhoid bacillus has been found in bone abscesses, 
in purulent meningitis, and other post-typhoidal suppurative foci. 



